Jun Dong
email: dongjun@zust.edu.cn

Yuanjun Tang

Ange Nzihou

Yong Chi

Key factors influencing the environmental performance of pyrolysis, gasification and incineration Waste-to-Energy technologies

Keywords:

Introduction

Waste-to-Energy (WtE) has played an important role in dealing with the increasing production of municipal solid waste (MSW) [START_REF] Carneiro | Energy, exergy, environmental and economic analysis of hybrid waste-to-energy plants[END_REF]. Stimulated by dwindling reserves of fossil fuels and sustainable energy production, WtE is seen as an attractive approach to recover energy and useful materials [START_REF] Tan | Energy, economic and environmental (3E) analysis of waste-to-energy (WTE) strategies for municipal solid waste (MSW) management in Malaysia[END_REF]. Today, approximately 1.5% of the total energy is provided by WtE in European Union (EU) [START_REF] Mayer | Critical review on life cycle assessment of conventional and innovative waste-to-energy technologies[END_REF]. In this context, the future goal of modern WtE has shifted from being a "waste treatment sector" to an "energy and resource producer" [START_REF] Arena | From waste-to-energy to waste-to-resources: the new role of thermal treatments of solid waste in the Recycling Society[END_REF].

Incineration is currently the most mature WtE technology with over 1400 plants in operation around the world [START_REF] Arena | A life cycle assessment of environmental performances of two combustion-and gasification-based waste-to-energy technologies[END_REF]. The last generation of incinerators is equipped with advanced air pollution control (APC) system, which has significantly improved their environmental performance [START_REF] Kumar | A review on technological options of waste to energy for effective management of municipal solid waste[END_REF]. Pyrolysis and gasification are newly developed WtE technologies [START_REF] Luz | Technoeconomic analysis of municipal solid waste gasification for electricity generation in Brazil[END_REF], which operate in the absence of oxygen (pyrolysis) or in the presence of sub-stoichiometric air (gasification) to yield syngas ahead of combustion (the process is called the "two-step oxidation"). Both processes offer opportunities to minimize the formation of dioxins and to integrate with high-efficient energy recovery devices (such as, gas turbines and gas engines). So far, pyrolysis/gasification-based WtE is still less applied on commercial scale, as around a hundred plants are reported to process MSW [START_REF] Panepinto | Environmental performances and energy efficiency for MSW gasification treatment[END_REF].

However, there remains a lack of consensus about a better WtE technology. From the perspective of environment, WtE should achieve lower emissions, a higher energy recovery efficiency, and efficient recovery of inorganic materials. Therefore, it is necessary to conduct a systematic comparison among various WtE technologies.

This targeted aim calls for support by suitable assessment tools. Life cycle assessment (LCA) represents a comprehensive methodology as it quantifies both direct and indirect environmental impacts of a system throughout its life cycle [START_REF] Astrup | Life cycle assessment of thermal wasteto-energy technologies: review and recommendations[END_REF][START_REF] Laurent | Review of LCA studies of solid waste management systems-Part II: Methodological guidance for a better practice[END_REF]. In the past years, increasing LCA studies have been performed in the field of WtE. Majority of these studies are focused on incineration, aiming at identifying potential environmental burdens [START_REF] Boesch | An LCA model for waste incineration enhanced with new technologies for metal recovery and application to the case of Switzerland[END_REF][START_REF] Lausselet | Life-cycle assessment of a Waste-to-Energy plant in central Norway: current situation and effects of changes in waste fraction composition[END_REF], or making comparisons with alternatives such as landfill [START_REF] Cucchiella | Sustainable waste management: Waste to energy plant as an alternative to landfill[END_REF][START_REF] Nabavi-Pelesaraei | Modeling of energy consumption and environmental life cycle assessment for incineration and landfill systems of municipal solid waste management -a case study in Tehran Metropolis of Iran[END_REF]. However, LCA of pyrolysis and gasification technologies is still scarcely assessed. Evangelisti [START_REF] Evangelisti | Life cycle assessment of conventional and two-stage advanced energy-from-waste technologies for municipal solid waste treatment[END_REF] evaluated three pyrolysis and gasification systems (gasification-plasma gas cleaning, pyrolysiscombustion, and gasification-combustion) and reported that gasification-plasma was the only system showing a better environmental performance over modern incineration. Zaman [START_REF] Zaman | Life cycle assessment of pyrolysis-gasification as an emerging municipal solid waste treatment technology[END_REF] in turn indicated that gasification-combustion appeared more optimal than incineration. The contradictory result to those of Evangelisti [START_REF] Evangelisti | Life cycle assessment of conventional and two-stage advanced energy-from-waste technologies for municipal solid waste treatment[END_REF] can be mainly due to different energy recovery efficiencies adopted in these studies. Arena [START_REF] Arena | A life cycle assessment of environmental performances of two combustion-and gasification-based waste-to-energy technologies[END_REF] compared operational data from a gasification-melting system with incineration and reported that incineration was better for most of the selected impact categories, though gasification could produce a less leachable residue with a greater potential to be recovered. Overall, as highlighted by Khandelwal [17] and Mayer [START_REF] Mayer | Critical review on life cycle assessment of conventional and innovative waste-to-energy technologies[END_REF] in recent reviews, a comparison of different WtE technologies requires further investigation to derive clearer results.

The inconsistencies in the available literature can be explained by issues of both WtE technical parameters and LCA modelling methodologies [START_REF] Astrup | Life cycle assessment of thermal wasteto-energy technologies: review and recommendations[END_REF]. From the technic perspective of WtE, existing studies revealed that parameters, such as plant energy efficiencies [START_REF] Trindade | Advanced exergy analysis and environmental assesment of the steam cycle of an incineration system of municipal solid waste with energy recovery[END_REF], air pollutants at stack [START_REF] Makarichi | The evolution of waste-to-energy incineration: a review[END_REF], waste composition [START_REF] Bisinella | Importance of waste composition for Life Cycle Assessment of waste management solutions[END_REF], and solid residues management [START_REF] Allegrini | Life cycle assessment of resource recovery from municipal solid waste incineration bottom ash[END_REF] were decisive for environmental performance. Besides, LCA principles, such as energy substitution [START_REF] Burnley | Factors influencing the life cycle burdens of the recovery of energy from residual municipal waste[END_REF], temporal and geographic horizon [START_REF] Doka | Life cycle inventories of waste treatment services[END_REF], and choices of impact assessment methods [START_REF] Lieberei | Resource depletion assessment of renewable electricity generation technologies-comparison of life cycle impact assessment methods with focus on mineral resources[END_REF] were also proven to be vital factors affecting the life cycle impacts. However, very few of the studies (i.e. only 6% of 315 peer-reviewed studies [START_REF] Mayer | Critical review on life cycle assessment of conventional and innovative waste-to-energy technologies[END_REF]) have addressed the holistic description of all these aspects, which has hindered transparent comparison and determination of a more sustainable WtE technology.

Consequently, this paper aims to give a systematic assessment of environmental profile of different WtE technologies. Within this context, first, an LCA modelling is conducted quantifying the environmental impacts of four WtE technologies, namely incineration, pyrolysis, gasification and gasification-melting. This is done based on data inventory from on-site operation of several representative plants. These technologies are the most common types of WtE currently available.

Then, the results are discussed by a comprehensive sensitivity analysis to seek crucial factors (i.e. input parameters, processes, operating conditions, and modelling assumptions), which drive their environmental sustainability. Finally, potential areas of improvement are outlined for each specific technology. Therefore, this paper contributes to already existing LCA and extends knowledge in the following ways: (1) quantifying the environmental performance of different WtE technologies, which fills the knowledge gaps in this field and also serves as a reference for other similar LCA studies; (2) carrying out a holistic sensitivity analysis of the LCA process, which identifies key environmental hotspots and bottlenecks of each WtE technology for future improvements;

(3) the results from this study are expected to increase the credibility and reliability of LCA, thus providing potentially useful recommendations for public policy and planning.

Methodology

Goal and scope definition

The life cycle assessment is performed following the ISO standards [START_REF]Environmental management-life cycle assessment-principles and framework[END_REF] and the International Reference Life Cycle Data System (ILCD) Handbook [START_REF]International Reference Life Cycle Data System (ILCD) Handbook -General Guide for Life Cycle Assessment -Detailed Guidance[END_REF]. The aim is to compare the environmental impacts of four representative WtE technologies, and then, to identify the key factors determining their sustainability as well as potential areas of improvements. The goal of this study is in accordance with the ''Situation C1′' as defined by the ILCD Handbook, and implies an "attributional" approach for LCA modelling. The LCA modelling is carried out by using the Gabi 8.0 software. Fig. 1 shows the system boundaries under consideration, which are split into foreground and background systems. The foreground system covers waste pre-treatment (required in several WtE units), thermal conversion (incineration, pyrolysis, gasification, or gasificationmelting), energy recovery, APC, and solid residues management. MSW collection and transportation before arriving the WtE plants are not included. All plants are assumed to be connected to steam turbine for energy recovery and are equipped with a typical APC line comprising selective non-catalytic reduction (SNCR), dry scrubber with slaked lime (Ca(OH) 2 ) and activate carbon, and bag filter for removing NO x , acid gases, dioxins, and particulate matter (PM). Solid residues include bottom ash, slag and APC residues. It is worth noticing that the bottom ash (generated in S1, and S3 scenarios) and slag (generated in S2, and S4 scenarios) are separately defined due to their different characteristics. The latter appears as a melted, vitrified material feasible for immediate recycling [START_REF] Tanigaki | Co-gasification of municipal solid waste and material recovery in a large-scale gasification and melting system[END_REF]. Instead, the bottom ash is assumed to be landfilled, which follows the common EU practice. APC residues mainly consist of fly ash and exhausted sorbents, and are stabilized before final disposal in landfill at a distance of 200 km. It should be mentioned that these settings are used in the baseline cases (default situation), while among these input parameters, the most critical ones will be discussed in detail based upon a sensitivity analysis, which is discussed in a later section 2.4.

Based upon the data from the Gabi databank, the background system quantifies the upstream production of ancillaries, as well as the benefits from recovered energy, metals and inerts. The plants are considered to produce electricity only. This assumption makes the modelling easier and would not affect the comparison results [START_REF] Arena | A life cycle assessment of environmental performances of two combustion-and gasification-based waste-to-energy technologies[END_REF]. In appliance with the attributional LCA, the ''multifunctional'' issue is addressed based upon the system expansion. The recovered electricity is assumed to substitute an equivalent amount of electricity from EU grid mix (25.8% nuclear, 21.5% coal, 19.7% natural gas, and 30.2% renewables, as par 2016 statistics) [START_REF]Energy Statistics, Energy datasheets: EU-28 countries[END_REF]. The recycling of metals is credited for avoiding the production of virgin metals. The recovered slag is used in road construction to substitute natural aggregates.

The functional unit is defined as the thermal treatment with electricity recovery of one tonne of MSW. The plants are assumed to be located in EU, and have a composition of the EU average residual waste (Table 1) [START_REF] Manders | Life Cycle Assessment of the treatment of MSW in "the average "European Waste-to-Energy plant[END_REF], and a lower heating value of 10.307 GJ/tonne according to the CEWEP report of 314 waste incineration plants in EU [START_REF] Reimann | CEWEP Energy Report III (status 2007-2010) -Results of Specific Data for Energy, R1 Plant Efficiency Factor and NCV of 314 European Wasteto-Energy (WtE) Plants[END_REF]. The elementary composition is determined for each waste fraction based on the study of Koehler [START_REF] Koehler | Probabilistic and technology-specific modeling of emissions from municipal solid-waste incineration[END_REF] (see Table S1 in Supplementary Material).

The LCA time frame for potential environmental impacts is considered to be 100 years. This is in particular relevance for the leaching of ash components in landfill, where emissions can last thousands of years [START_REF] Astrup | Life cycle assessment of thermal wasteto-energy technologies: review and recommendations[END_REF][START_REF] Boesch | An LCA model for waste incineration enhanced with new technologies for metal recovery and application to the case of Switzerland[END_REF]. A long-term perspective covering a time span of 60,000 years will be discussed in the sensitivity analysis, which is based upon recommendations of Doka [START_REF] Doka | Life cycle inventories of waste treatment services[END_REF].

Data source and inventory analysis

The LCA modelling is processed using mass and energy balances, which is based upon the material and substance flow analysis (MFA/ SFA) for each WtE system. The incoming waste can end up in any of the compartments, including bottom ash (or slag), APC residues, or airborne emissions. Transfer coefficients (TCs) express the proportion of each input element constituting the waste. The source and data used to compute TCs are detailed in the Supplementary Material (Section SM-2). Fig. 2 shows the mass flow sheets in the four analysed WtE systems.

The data used are mainly based on on-site operation of several reference plants. The selected plants are all industrial-scale, and therefore, are capable of reflecting reliable and representative performance of specific WtE technologies. Basic information of the reference WtE plants is provided in Table 2. It is worth noticing that the selected gasification-melting plant is located in Japan, which may result in a different waste composition from that in EU. However this would not cause significant effects on the operating of gasification-melting process, such as coke consumption [START_REF] Tanigaki | A case-study of landfill minimization and material recovery via waste co-gasification in a new waste management scheme[END_REF]. The life cycle inventory is summarized in Table 3, while the description of each scenario is detailed as follows.

S1: Incineration

The modelled incineration reflects moving grate incinerator, which is the predominant type used worldwide [START_REF] Makarichi | The evolution of waste-to-energy incineration: a review[END_REF]. TCs for incineration are adapted from the work of Koehler [START_REF] Koehler | Probabilistic and technology-specific modeling of emissions from municipal solid-waste incineration[END_REF]. The process conditions are sourced from the average performance of 110 incineration plants (85% of the total number) operating in France [START_REF] Beylot | Environmental impacts of residual Municipal Solid Waste incineration: a comparison of 110 French incinerators using a life cycle approach[END_REF][START_REF] Beylot | Municipal Solid Waste Incineration in France: An Overview of Air Pollution Control Techniques, Emissions, and Energy Efficiency[END_REF]. Therefore, the data are representative of incineration in other regions with similar technology levels.

Air emissions are divided into two categories, namely the wastespecific and process-specific emissions. Waste-specific emissions are dependent on waste input and are calculated using TCs. Two pollutants (CO 2,fossil and Hg) are compiled considering the availability of TCs relative to each WtE system. Process-specific emissions are controlled by thermal technologies and/or APC operation. Seven pollutants (CO, dioxins, HCl, NH 3 , NO x , PM and SO 2 ) are considered, which are calculated using emission factors based on French incinerators.

Incineration enables the recovery of energy and materials. A net electricity recovery efficiency of 17.7% is used, which is reported by CEWEP as an average value for the selected incineration plants in EU [START_REF] Reimann | CEWEP Energy Report III (status 2007-2010) -Results of Specific Data for Energy, R1 Plant Efficiency Factor and NCV of 314 European Wasteto-Energy (WtE) Plants[END_REF]. The mass and composition of bottom ash and APC residues are calculated using TCs. Scrap metals in the bottom ash can be recovered using mechanical separation. The processing steps and associated energy consumptions are sourced from the work of Allegrini [START_REF] Allegrini | Life cycle assessment of resource recovery from municipal solid waste incineration bottom ash[END_REF]. A typical recovery efficiency of 80% is used for ferrous (Fe) scraps [START_REF] Boesch | An LCA model for waste incineration enhanced with new technologies for metal recovery and application to the case of Switzerland[END_REF]. While the recovery of non-ferrous scraps varies with technologies, Aluminium (Al) recovery with a typical efficiency of 30% is considered [START_REF] Boesch | An LCA model for waste incineration enhanced with new technologies for metal recovery and application to the case of Switzerland[END_REF]. The remaining bottom ash is landfilled, whereas the modelling of the leaching of ash elements is taken from the work of Doka [START_REF] Doka | Life cycle inventories of waste treatment services[END_REF]. The APC residues are assumed to be chemically stabilized by the Ferrox process. A detailed assessment of the associated impacts is estimated according to Fruergaard [START_REF] Fruergaard | Life-cycle assessment of selected management options for air pollution control residues from waste incineration[END_REF].

S2: Pyrolysis

The modelling of pyrolysis is based on rotary kiln, which is the only type of reactor that has successfully achieved industrial-scale implementation [START_REF] Czajczyńska | Potential of pyrolysis processes in the waste management sector[END_REF]. The basic processes and data are calculated from the reference plant "Burgau" in Germany [START_REF] Stein | Review of Small Scale Waste Conversion Systems[END_REF], which had operated for over 30 years (until 2015) and is a good example of full-scale pyrolysis. The associated TCs are approximated based upon the work of Arena and Di Gregorio [START_REF] Arena | Element partitioning in combustion-and gasification-based waste-to-energy units[END_REF], which have been adapted considering data of air emissions in the reference plant.

The incoming waste is shredded to 300 mm size as a pre-treatment step, and is then fed into the rotary kiln together with around 12-20 kg of quicklime per tonne of waste [START_REF]Waste pyrolysis plant "Burgau[END_REF]. The kiln is externally heated using a "Other/inert waste" may include amounts of combustibles that not elsewhere classified. However due to the lack of data, this composition is treated as a whole as non-combustible. combustion flue gas to maintain the core reaction zone at about 500 °C. Pyrolysis is carried out with an average residence time of 1 h, due to which, the waste is converted into gas and char fractions. The gas is conveyed to a downstream combustor, which operates at 1200 °C. The solid fraction undergoes separation to extract metals. Their recovery efficiencies are assumed to be same as those of incineration. The remaining char in Burgau plant is not utilized and is transported to landfill. However, it should be noted that this reference plant was designed for pure disposal purpose at the time of planning. Since the aim of this study is to examine the waste-to-energy potential of different Letters "I" and "E" represent respectively "import" and "export".

technologies, proper utilization of this high-caloric char should be considered, as it would have a significant impact on the overall energy efficiency. As a result, char is assumed to be milled to fine powders, and combusts along with syngas, following common practices in similar plants (such as, Siemens, Mitsui, and Takuma). The temperatures of the combustion chamber are sufficiently high, which generates a molten slag. As mentioned previously, the slag can have a superior leaching resistance, due to which, it is regarded as a recyclable material for road construction application.

S3: Gasification

The modelling of gasification is based on the operation of reference plant "Kymijärvi II" in Finland [START_REF] Savelainen | Kymijärvi II plant: High-efficiency use of SRF in power production through gasification[END_REF], which uses circulating fluidized bed gasifier and is the largest gasification plant processing MSW-derived fuels (namely, solid refuse fuels; SRF) in the world. The TCs have been estimated based on the studies of Konttinen [START_REF] Konttinen | Trace element behavior in the fluidized bed gasification of solid recovered fuels-a thermodynamic study[END_REF] and Arena and Di Gregorio [START_REF] Arena | Gasification of a solid recovered fuel in a pilot scale fluidized bed reactor[END_REF].

The MSW is upgraded (through shredding, and pelletization) to accord with the required quality of SRF. Such processing requires energy and the data are taken from Nasrullah [START_REF] Nasrullah | energy and material balances of SRF production process. Part 3: Solid recovered fuel produced from municipal solid waste[END_REF]. Then, the waste passes into the gasifier, which operates at 850-900 °C to generate syngas. This is followed by gas cleaning, for which the produced gas is cooled in a heat recovery unit the temperature drops down to 400 °C. After this, the gas passes through a series of ceramic filters to remove alkalis, heavy metals and PM. The cleaned syngas has few corrosive contaminants, which enable it to produce high-quality steam (540 °C, and 121 bar). This steam quality is higher than those produced in conventional incineration plants (40 bar, 400 °C) [START_REF] Wood | Review of state-of-the-art waste-to-energy technologies[END_REF]. Consequently, the plant reaches an electricity recovery efficiency of 27.4% (net efficiency) [START_REF] Savelainen | Kymijärvi II plant: High-efficiency use of SRF in power production through gasification[END_REF]. The produced bottom ash appears similar to that from the incineration case, which is landfilled after recycling of the metals.

S4: Gasification-melting

The Direct Melting System, which has achieved commercial operation for more than 30 years in Japan and South Korea, is selected as a representative gasification-melting system. The performance data are mainly sourced from a reference plant in Japan, which is one of the world's largest gasification-melting plants [START_REF] Tanigaki | Co-gasification of municipal solid waste and material recovery in a large-scale gasification and melting system[END_REF][START_REF] Tanigaki | A case-study of landfill minimization and material recovery via waste co-gasification in a new waste management scheme[END_REF][START_REF] Tanigaki | Operating and environmental performances of commercial-scale waste gasification and melting technology[END_REF]. The TCs are taken from Arena and Di Gregorio [START_REF] Arena | Element partitioning in combustion-and gasification-based waste-to-energy units[END_REF] based on a similar prototype.

The MSW does not require pre-treatment. It is fed into the shaft furnace together with coke (to assist ash melting) and limestone (to adjust the viscosity of melt). Gasification occurs in the middle zone of the furnace (600-800 °C) and the produced syngas is sent for complete burning in a downstream combustor. Incombustible waste fractions descend to the bottom of furnace, where combustion and melting reactions occur with the injection of O 2 -rich air (36 vol% O 2 ) at 1000-1800 °C. Molten residues are discharged intermittently and separated magnetically into slag and metals. The net electricity recovery efficiency reaches 16.7% by subtracting the internal power consumption, such as oxygen generator and ash melting [START_REF] Tanigaki | A case-study of landfill minimization and material recovery via waste co-gasification in a new waste management scheme[END_REF].

Life cycle impact assessment

The life cycle impact assessment (LCIA) is estimated according to the CML 2001 method, updated in August 2016. A total of 11 impacts including both toxic and non-toxic categories are considered: global warming (GWP), acidification (AP), eutrophication (EP), ozone layer depletion (ODP), photochemical ozone creation (POCP), terrestric ecotoxicity (TETP), freshwater aquatic ecotoxicity (FAETP), human toxicity (HTP), marine aquatic ecotoxicity (MAETP), and abiotic depletion (ADP elements and ADP fossil). The accounting of biogenic CO 2 emissions (as opposed to CO 2 where the carbon is of fossil origin) are widely debated. In this study, biogenic CO 2 is treated carbon neutral (GWP of zero), following currently common LCA practice [START_REF] Christensen | C balance, carbon dioxide emissions and global warming potentials in LCA-modelling of waste management[END_REF][START_REF] Flórez-Orrego | Comparative exergy and economic assessment of fossil and biomass-based routes for ammonia production[END_REF].

Sensitivity analysis

The sensitivity analysis is conducted using the method recommended by Clavreul [START_REF] Clavreul | Quantifying uncertainty in LCA-modelling of waste management systems[END_REF]. The objective is to systematically identify key factors influencing the environmental performance of different WtE systems. The following steps have been applied successively.

• Perturbation analysis identifies important individual parameters to overall results, whereby all input parameters are varied one at a time by 10% by the following equation: APC = air pollution control, PM = particulate matter a The raw MSW need to be shredded as pre-treatment in pyrolysis scenario (S2), which necessarily requires electricity. The consumption amount, together with the energy required for char milling, has been quantified as a whole (i.e. internal energy use, assumed to be 20% of the total recovered electricity).

= SR result initial result parameter initial parameter ∆ ∆ (1)
b The value presents the net amount of bottom ash after metals separation, which is destined to be landfilled. c Biogenic CO 2 emissions are considered neutral to GWP. The fraction of biogenic carbon based on EU average MSW composition is estimated at 48% according to IPCC guideline.

d The PM emission is divided into 99.5% PM 2.5 and 0.5% PM 2.5-10 according to Doka [START_REF] Doka | Life cycle inventories of waste treatment services[END_REF], with the aim to better quantify its impact on human and ecosystem. S8). Parameters with a higher absolute SR represent that they have more significant influence on the overall results. Parameters with SR values higher than 0.2 will be further discussed.

• Several process operating conditions are then discussed based upon the scenario analysis. The aim is to examine if an alternative choice for the construction of scenarios would vary the ranking of WtE systems or not.

• The last part of the sensitivity analysis addresses model assump- tions. From the methodological point of view, the LCA results typically depend on various choices. Three critical aspects, namely the substituted energy sources, the choice of a functional unit, and the choice of time frame, are discussed herein.

Results

The overall environmental impacts of the baseline WtE systems are shown in Fig. 3. All the four systems exhibit negative values for 8 out of 11 impacts, indicating an environmental benefit due to credits from the recovery of energy and materials. Contrarily, positive values of GWP, EP and TETP impacts indicate environmental burdens. Comparing different WtE technologies, gasification (S3) is better for 5 impacts (GWP, AP, POCP, TETP, and ADP fossil). Gasification-melting (S4) instead has the lowest impacts in 4 categories (EP, ODP, FAETP, and ADP elements), whilst pyrolysis (S2) is superior for HTP.

In order to identify main sources of the environmental burdens, contribution analysis is conducted to distribute the overall impacts into different life cycle stages. Fig. 4 reports the results refer to 7 selected categories that are representative in terms of non-toxic impacts, toxic impacts and resources depletion. It is observed that the impacts from "stack emissions", "energy recovery" and "metals recycling" are the most noteworthy contributors, with the former one being an environmental loading and the latter two being environmental savings. The "stack emissions" account for a large proportion of the GWP, AP, EP and TETP impacts. For all WtE systems there is a positive impact of GWP, which is mainly due to the fossil-origin CO 2 emission derived from MSW. S1, S2 and S3 scenarios show negligible difference of GWP stack emissions (417-420 kg CO 2 eq.), while that value in S4 is much higher (602 kg CO 2 eq.) due to the burning of coke to maintain high temperature in the melting zone of the gasifier [START_REF] Tanigaki | Co-gasification of municipal solid waste and material recovery in a large-scale gasification and melting system[END_REF]. By contrast, S4 shows a significantly lower AP and EP emissions at stack, of which NO x emission is the principal contributor. The reduced impacts can be ascribed to the following two reasons. Firstly, the emissions data in specified WtE plants are broadly comparable with the exception of NO x (Table 3), of which S4 shows the lowest NO x emission. Secondly, pyrolysis and gasification WtE produces a lower flue gas volume as a consequence of the lower excess air (ER = 1.2 vs. ER = 1.6 in S1). Hence, mass emission rate per tonne of MSW is decreased compared with incineration. Lastly with respect to TETP, heavy metals (here only Hg is considered) are the major contributors. S3 shows the least impact due to intermediate gas cleaning that has condensed part of the metals in the filter.

"Energy recovery", due to the substitution of fossil fuels combustion for electricity production, has made a significant contribution to reduce GWP, AP, EP and ADP fossil impacts. The highest avoided emissions are found in S3. As has been mentioned previously, the use of intermediate syngas purification offers the opportunity to remove targeted pollutants (particularly Cl) prior to combustion. In this case, the steam data of the boiler reach 121 bar and 540 °C, thus improving the efficiency of the power cycle (a net efficiency of 27% in S3 vs. 18% in S1). On the other hand, S4 shows the lowest amount of electricity recovered. This is because the ash melting process is quite energy intensive, which consumes about 24% of the gross electricity generated. However, the main advantages of melting are size reduction of the ash to be landfilled and the decrease of toxicity (dioxins and heavy metals leaching) [START_REF] Leckner | Process aspects in combustion and gasification Waste-to-Energy (WtE) units[END_REF].

"Metals recycling" shows also avoided impacts, in particular for toxicity impacts (FAETP, HTP). Recycling of Fe is the main contributor to FAETP credits (greater than96%), while HTP credits are nearly completely ascribed to Al recycling. This indicates that the environmental impacts from scrap metals separation, upgrading, and reprocessing are considerably lower than their production from virgin materials [START_REF] Boesch | An LCA model for waste incineration enhanced with new technologies for metal recovery and application to the case of Switzerland[END_REF]. With reference to the four WtE scenarios, the composition of recycled metals is strongly different, mainly as oxidized form in incineration and metallic form in pyrolysis and gasification. Higher actual recovery efficiencies and subsequently increased avoiding impacts are thus possible in pyrolysis/gasification-based WtE. However, S3 shows lower FAETP and HTP credits due to higher transfer of metals to fly ash (see Table S4).

"Materials and energy provision" have only a minor contribution to S1 and S2 scenarios, however is more noteworthy in S3 and S4. For S3 this contribution mainly derives from the energy demand to produce SRF, as pre-treatment to upgrade the quality of the incoming waste. For S4 the use of coke appears significant to ADP fossil impact as a consequence of resource use for its production, but also contributes to GWP, AP and EP during its utilization. "Bottom ash landfill" accounts for a greater contribution to FAETP impact in S1 system, to a less extent in S3, due to the consumption of energy for mechanical treatment and the subsequent leaching of heavy metals within the considered time frame. On the other hand, the impacts resulting from "bottom ash landfill" are absent in S2 and S4 scenarios, being substituted by an avoided contribution from "slag recycling", despite that this benefit is insignificant. As for the rest life cycle stages regarding "transportation" and "APC residues stabilization and landfill", they account for an insignificant contribution to all impact categories.

Overall, the contribution analysis has identified key processes contributed to the environmental impacts of each WtE system. Based on the results, a sensitivity analysis is conducted. In the following, the effects of key input parameters, operation conditions, and LCA modelling conditions are separately discussed in Section 3.1, 3.2, and 3.3. Finally, the "best-case" scenarios are discussed in Section 3.4. Fig. 6. The effect of improved air pollution control process on the environmental impacts of incineration (S1) WtE technology. Suffix letter "APC" stands for alternative "Air Pollution Control" option. Some impacts are scaled to fit the y-axis; their original values can be obtained by dividing the factor shown on the x-axis.

Table 4

The effect of bottom ash recycling in road construction on the environmental impacts of incineration (S1) and gasification (S3) WtE technologies. a Suffix letter "BA recycling" stands for "Bottom Ash recycling" in in specified scenarios. b Grey row named "variation" represents the relative change of environmental impacts in BA recycling case to those in the base case. Only absolute values are presented because all the environmental impacts are decreased in BA recycling case.

Importance of key input parameters to the LCA results

The critical parameters, which significantly affect the LCA results, have been identified through a perturbation analysis. The results are illustrated in Fig. 5 in terms of SR values for seven selected impact categories. The results show that, among the 40-60 input parameters in each WtE system, around 15 parameters have SR values higher than ± 0.2. This means that, a 10% change in these parameters would lead to a variation of results larger than 2%.

Energy recovery efficiency is seen to be the most influential parameter for all WtE technologies. The highest SR value of 22.9 is seen for EP of S4. Parameters related to the properties of feedstock, in particular the lower heating value of incoming waste and CO 2,fossil stack emission, also stand out in all impact categories. These parameters are mainly dependent on waste composition, which highlight a relatively important role of feedstock variability in determining the total results. NO x stack emission is also an important parameter, and is a result of the waste properties (N content), combustion technology and the effectiveness of APC system. To a lesser extent, Hg and NH 3 emissions influence TETP and EP, respectively. Other key parameters are mainly related to metals recycling, for example, the amount of metal elements transferred to dedicated fractions (bottom ash in S1 and S3, or char in S2, or molten metals in S4), and their recovery efficiencies. In addition, some parameters are of importance to only specified systems. Examples of such parameters include internal electricity consumption in S2 and S3, and slag and APC residues management in S4. In summary, key parameters determining the environmental performance of WtE technologies are found to be as follows:

• An effective energy recovery is a relatively important parameter, at the same time, efforts should be paid to decrease as much as the internal energy consumption.

• The variation in feedstock plays a crucial role in determining the waste composition (such as, C-fossil and N content) and its heating value.

• An efficient air emissions control system is an important factor, and this is particularly true for NO x removal.

• Metals recycling is also a key parameter and contributes to both non-toxic and toxic impacts.

Importance of operating conditions to the LCA results

Effectiveness of air pollution control

The results from the contribution analysis (Fig. 4) demonstrate a crucial role of stack emissions to final environmental burdens. Due to this reason, the effectiveness of APC process is discussed in this work. In the base case, the APC line in each WtE system is based on "SNCR + dry Ca(OH) 2 scrubber + activate carbon". Today, with gradually tightened emission standards, more effective APC techniques have been put in use [START_REF] Vehlow | Air pollution control systems in WtE units: An overview[END_REF]. As a potential improvement, the use of "wet Ca(OH) 2 scrubber + activate carbon + SCR" is evaluated. Detailed description of the APC techniques and operating data are provided in the Supplementary Material. Furthermore, the results for incineration case are discussed in Fig. 6. As expected, the related assumptions have led to a better environmental performance in S1-APC scenario, particularly in terms of AP, EP and POCP, which show a decrease of 99%, 113% and 39% as compare to S1, respectively. Compared to the results presented in Fig. it is observed that AP, EP and POCP impacts of S1-APC Fig. 7. The effect of applying pyrolysis char in land as soil amendment on the environmental impacts of pyrolysis (S2) WtE technology. Suffix letter "LA" stands for "Land Application" of the pyrolysis char. Some impacts are scaled to fit the y-axis; their original values can be obtained by dividing the factor shown on the x-axis.

scenario have surpassed pyrolysis and gasification scenarios (S2-S4) and become the most environmental-friendly scenario. As indicated previously in Fig. 5, this benefit is mainly due to the decreased NO x emission, and to a lesser extent, due to the decreased SO 2 , HCl and NH 3 emissions.

Based upon this analysis, implementation of a more effective APC process can significantly reduce the overall environmental impacts, thus determining the relative sustainability of different WtE systems.

Bottom ash recycling

The results shown in Fig. 4 indicate varied environmental impacts from "bottom ash landfill" (in S1 and S3) and "slag recycling" (in S2 and S4) processes. The former is seen as an environmental burden due to the consumption of energy in landfill operation and leaching of toxic substances. Realizing that bottom ash shows similar technical properties to those of natural aggregates, increasing efforts are taken to utilize bottom ash in road construction in many EU countries [START_REF] Gianfilippo | LCA of management strategies for RDF incineration and gasification bottom ash based on experimental leaching data[END_REF][START_REF] Astrup | Pretreatment and utilization of waste incineration bottom ashes: Danish experiences[END_REF]. For this reason, the "bottom ash recycling" case is assessed in this work. Key data used for model estimation are detailed in the Supplementary Material, and the results are presented in Table 4.

Compared with the base case, assumptions on bottom ash recycling have resulted in decreased impacts for all categories. The benefits are mainly derived from the following factors: (1) decrease in energy consumption associated with ash landfill, (2) reduction in the provision of natural gravel. Incineration (S1-BA recycling) generally shows more sustainable impacts than gasification (S3-BA recycling), which is due to a higher amount of bottom ash generated and being recycled. However, the results show that the effect of bottom ash recycling is quite marginal, which does not change the overall ranking of different WtE systems. Similar findings were drawn by Birgisdottir [START_REF] Birgisdottir | Life cycle assessment of disposal of residues from municipal solid waste incineration: recycling of bottom ash in road construction or landfilling in Denmark evaluated in the ROAD-RES model[END_REF], who report fairly equal environmental impacts for recycling or landfill of incineration bottom ash. The results on the other hand indicate that recycling can serve as a potential future management option for bottom ash, which in fact would be preferred over landfill as a means for conserving resources. For this option, the limitation lies within the leaching emissions, as has recently been assessed by Allegrini [START_REF] Allegrini | Life cycle assessment of resource recovery from municipal solid waste incineration bottom ash[END_REF] that road application of bottom ash may potentially lead to higher release of toxic substances.

Pyrolysis char utilization in land application

In the base case, char generated from pyrolysis is used as an energy source for electricity recovery. Comparatively, char applied in land is considered in this work. The LCA boundary of the char application process consists of char transport to dedicated farms, spreading it on soil, and the subsequent effects to soil. While energy utilization of char in the base case avoids electricity production, the land application of char provides several merits, including substitution of mineral fertilizers (N, P and K), and long-term carbon sequestration. Detailed calculation is available in the Supplementary Material. Fig. 7 shows the associated environmental impacts along with those from the base case. Char utilization in land shows higher saved impacts regarding GWP, AP and EP, and to lesser extent for ODP and POCP. Looking at the contribution of each life cycle stage, majority of the reduced impacts are associated with the decreased stack emissions, which is due to the exempted char combustion. The benefit is also reflected by a negative contribution from the avoided production of mineral fertilizers, particularly for AP and EP. Conversely, the land application case significantly increases toxic impacts, such as TETP, FATEP and HTP, which is mainly due to metal emissions, and originally contained in char yet transferred to soil.

In short, the utilization pathway of pyrolysis char would greatly influence the environmental performance of pyrolysis (S2) system. Overall, it is difficult to figure out which application option is more favourable. However, critical life cycle hotspots can be identified. For example, it is important to consider the potential risk of metal contaminants if char is to be used in land. This requires efforts to reduce the concentrations of metals in char, or modify them to become less reactive. Overall, there is a need to carefully address the potential burdening impacts, so as to properly determine a better utilization route for char.

Importance of model conditions to the LCA results

Substituted energy sources

In the base case, the electricity produced is assumed to substitute the one provided by the EU grid mix. Concerning the importance of energy recovery process, alternative energy sources in individual countries are considered as substituted options, and these countries include Czech, Italy, France, and Denmark. These countries are selected because electricity from Czech is "dirtier" based on higher utilization of coal (50.4%). The French and Italian grid mixes are instead "cleaner" due to a predominant role of respectively nuclear (72.5%) and natural gas (44.5%) in their energy infrastructures. However, a higher ratio of renewables (60.5%) is observed for Denmark's energy infrastructure [START_REF]Energy Statistics, Energy datasheets: EU-28 countries[END_REF].

The results for GWP impact are shown in Fig. It is noted that the sources of substituted electricity heavily affects the LCA results. GWP under different substituted energy sources is found to be in the following descending order: France > Denmark > EU grid mix > Italy > Czech. This is due to the reason that, more the electricity is produced based on fossil fuels, higher are the GWP emissions, thus allowing increased environmental credits. The overall ranking of WtE systems changes, which means that GWP from incineration (S1) outperforms gasification (S3), provided the displaced electricity is based on French grid mix. This can be explained by the higher amount of electricity recovered from S3, which is more sensitive to the source of energy to be substituted.

These results are in accordance with the previous findings [9, [START_REF] Turconi | Life cycle assessment of waste incineration in Denmark and Italy using two LCA models[END_REF][START_REF] Bassi | Environmental performance of household waste management in Europe -An example of 7 countries[END_REF]. The results highlight that, the assumptions on the substituted energy should be adequately addressed. For example, the geographical location of the specified plant has a certain significance, especially when the aim is to select an environmentally optimal WtE technology.

Alternative functional units

The robustness of LCA results is tested by changing the perspectives of functional unit. The "input-oriented" functional unit in the base case (i.e. 1 tonne of MSW) is shifted to two alternative "output-oriented" ones, as follows: (1) 1 kwh of electricity generated, and (2) 1 kwh of exergy in the output products. The calculation data are provided in the Supplementary Material.

Fig. 9 shows generally decreased impacts across all categories, which are 2-3 orders of magnitude less than the base case. This is expected, as from the input-oriented perspective, the treatment of 1 tonne of MSW can result in around 500-800 kwh of electricity generation. Changing the functional unit has altered the ranking of different scenarios. An improved performance is observed for incineration (S1-FU2, S1-FU3) regarding HTP, MAETP and ADP fossil impacts, and gasification-melting (S4-FU2, S4-FU3) regarding AP and POCP impacts. This can be explained by the differences of energy efficiencies. Gasification (S3) and pyrolysis (S2) produce higher amount of electricity and exhibit greater avoided (negative) impacts from the input-oriented perspective. However, this benefit is offset if the functional unit is fixed at an identical amount of electricity or exergy output. The results also show that the delivery of 1 kwh of electricity (Fig. 9a) or 1 kwh of exergy (Fig. 9b) has little difference in environmental impacts, which is due to the reason that exergy contained in the recovered electricity has contributed to a majority proportion (87-95%) of the total output products. Overall, this analysis confirms that changing the functional unit in LCA would result in different environmental performance. The comparison of different WtE systems requires a very cautious selection of input or output perspective in order to properly interpret the results.

Long-term time frame

The time frame considered in this study is 100 years, which follows the common practice observed within the LCA. However, it is necessary for the sensitivity analysis to consider a long-term time frame, which aims at quantifying the "worst case" environmental consequences.

The analysis is focused on bottom ash after it is landfilled, and therefore, is relevant only for incineration (S1) and gasification (S3) systems. The long-term perspective considers 60,000 years, using TCs of substance leaching sourced from Doka [START_REF] Doka | Life cycle inventories of waste treatment services[END_REF]. The resulted environmental impacts are listed in Table 5. As expected, increased burdens are shown when expanding the time frame. This affects mainly the toxicrelated impacts, together with EP, which are ascribed to accumulated leaching of heavy metals. Among all categories, FAETP and MAETP are considerably more sensitive, particularly FAETP impact is shifted from an environmental saving to a burden, which has significantly deteriorated the performance of incineration and gasification cases.

"Best-case" scenarios

Finally, two "best-case" scenarios are modelled. The aim is to examine the performance of most state-of-the-art WtE technologies.

For incineration (S1), the operating data from AEB plant in Amsterdam are analysed [START_REF] Wood | Review of state-of-the-art waste-to-energy technologies[END_REF]. Due to innovative optimizations, such as increasing steam parameters (440 °C, 125 bar), use of steam reheating and water-steam cycle, and flue gas recirculation, the net energy efficiency of the plant reaches 30.6%, which is the highest among world's incineration plants. The APC employs "SNCR + activate carbon + wet Ca(OH) 2 scrubber" to control stack emissions (see details in the Supplementary Material). The plant also recycles various residual materials. The results shown in Fig. 10 confirm an improved environmental performance from the use of this Best Available Technology (BAT). All impacts from SI-BAT case show 4-229% decrease compared

Table 5

The effect of using alternative long-term time frame (60,000 years) on the environmental impacts of incineration (S1) and gasification (S3) WtE technologies. Legend with dark grey indicates a high changing of the impacts, light grey low and white with no changing. a Suffix letter "LT" stands for "Long-Term" time frame in specified scenarios.

to the base case (S1). The SI-BAT case has effectively surpassed S2, S3 and S4, showing the lowest impacts regarding 6 out of 11 categories (GWP, AP, EP, POCP, MAETP and ADP elements). This reveals that modern incineration has the potential to fulfill an environmentally sound technology, over pyrolysis and gasification at present. For gasification (S3), the "best-case" scenario is not dedicated to examining the performance of an alternative plant. Instead, the potential of the co-firing of cleaned syngas in existing boilers is assessed. This option represents one of the future perspectives for gasification due to several reasons [START_REF] Hrbek | Status report on thermal biomass gasification in countries participating[END_REF][START_REF] Vainikka | Waste firing in large combustion plants[END_REF]: (1) cleaned syngas connected to for example a coal-fired boiler allows the use of high steam parameters, thus exhibiting a huge potential to improve energy recovery efficiency;

(2) the introduction of gas instead of solid fuels into boilers can minimize problems related to correction, fouling, and ash quality; (3) the utilization of existing infrastructure can reduce the requirements for additional investment. For these purposes, S3-BAT scenario considers that the syngas produced from gasification is sent for co-firing in a coal plant, and assumes a net electricity efficiency of 35.4% based on the value of EU average [START_REF]Energy Efficiency Indicators: Efficiency of coal-fired power plant (Year: 2014)[END_REF]. The results presented in Fig. 10 show that S3-BAT scenario provides a superior performance with regards to 6 out of 11 impacts (GWP, AP, POCP, TETP, ADP elements and ADP fossil) when compared with the four WtE base cases. This again verifies the importance of boosting energy efficiency.

Discussion and future recommendations

The comparison among four most common WtE technologies, namely incineration (S1), pyrolysis (S2), gasification (S3), and gasification coupled with ash melting (S4), indicates an overall sustainable performance of all considered systems, which means that 8 out of 11 impacts show net environmental benefits. The impacts are much lower than those from the EU grid mix. For example, for the generation of 1 kwh of electricity, WtE technologies have the potential to reduce 18-68% of GWP (except for S4) by avoiding coal and natural gas. A brief calculation is conducted from a much broader perspective of functional unit, and assumes that the WtE plants are dedicated to managing 2,000 t/d of residual waste, which is a typical treatment capacity by a good sized metropolitan city [START_REF] Ripa | The relevance of site-specific data in Life Cycle Assessment (LCA). The case of the municipal solid waste management in the metropolitan city of Naples (Italy)[END_REF]. In such a case, 23,000-130,000 tonnes of GWP emissions per year could be avoided from the EU grid mix, which are equivalent to 16,000-25,000 tonnes of coal and 12-19 million m 3 of natural gas. This fact clearly indicates the huge potential for future development of WtE technologies.

The results from both contribution analysis (Fig. 4) and perturbation analysis (Fig. 5) confirm that energy recovery efficiency is one of the most critical parameters affecting the environmental performance of WtE technologies. The results presented in Fig. 10 further reveal the importance of improving plant efficiency in determining the relative ranking of each technology. This clearly indicates potential future areas for development. For incineration, positive experience gained from Amsterdam's AEB plant could serve as the basis of a number of technical optimisations designed to improve energy efficiency. For pyrolysis and gasification, a feasible application would be the use of syngas in existing power stations or other industrial plants, where the process could benefit from higher efficiency of host plants. Potential long-term development of pyrolysis and gasification includes the use of more efficient equipment, such as a combined cycle gas turbine [START_REF] Arena | Process and technological aspects of municipal solid waste gasification. A review[END_REF]. However, this application has not yet matured enough to meet the market demand.

The results from this study show developing attractiveness for pyrolysis and gasification WtE technologies. However, these technologies are still less commercialized at present. One important obstacle is associated with the variability of feedstock, as the applications of pyrolysis and gasification to WtE are often limited to few specific waste fractions (such as, SRF, plastic, and rubber tyres [START_REF] Lombardi | A review of technologies and performances of thermal treatment systems for energy recovery from waste[END_REF]). Factually, a higher degree of pre-treatment is generally required, even if some gasification technologies are able to accept raw MSW (for example, S4 system in this study). Therefore, improving the fuel quality seems important to reduce as much as of energy consumed for waste segregation, drying, and homogenization. A feasible approach could be to integrate the plants with an upstream material recovery facility, or mechanical biological treatment plants. Besides, waste pre-processing before WtE is also efficient for incineration, as is shown in Fig. increasing the waste lower heating value enables a higher recovery of electricity to effectively decrease the associated environmental burdens.

Energy, environment, economic, and social performance of WtE technologies are all of great interest to authorities [START_REF] Tan | Energy, economic and environmental (3E) analysis of waste-to-energy (WTE) strategies for municipal solid waste (MSW) management in Malaysia[END_REF][START_REF] Nabavi-Pelesaraei | Prognostication of energy use and environmental impacts for recycle system of municipal solid waste management[END_REF]. Therefore, a brief discussion of economic aspect is conducted in this work. It is evident that an accurate cost estimation and fair comparison among different WtE technologies cannot be addressed. This is due to a variety of issues, such as: (i) lack of sufficient operational data; (ii) variations in Fig. 10. The effect of using Best Available Technology in incineration (S1) and gasification (S3) WtE technologies. Suffix letter "BAT" stands for "Best Available Technology". Some impacts are scaled to fit the y-axis; their original values can be obtained by dividing the factor shown on the x-axis. regional energy cost, availability of resources; (iii) variations in governmental regulations and incentives [START_REF] Mayer | Critical review on life cycle assessment of conventional and innovative waste-to-energy technologies[END_REF]. Despite this fact, a detailed literature review of the cost structure of WtE technologies shows comparable annual capital and net operational cost between incineration and pyrolysis/gasification [START_REF] Ouda | Waste to energy potential: a case study of Saudi Arabia[END_REF]. Several studies [START_REF] Jadhao | Bury, burn, or gasify: assessing municipal solid waste management options in Indian megacities by exergy analysis[END_REF][START_REF] Rizwan | Optimal processing route for the utilization and conversion of municipal solid waste into energy and valuable products[END_REF] have shown that the net cost from gasification plants can even be lower than that from incineration, which is due to the higher efficiency of gasification that allows for a higher revenue from the export of electricity. Apart from these spatial and temporal factors, scale effects should also be accounted for when different WtE options are compared. This is due to the reason that an increasing plant size can lead to a drop in treatment cost [START_REF] Mayer | Critical review on life cycle assessment of conventional and innovative waste-to-energy technologies[END_REF].

To conclude, a range of critical input parameters, processes, operating conditions and modelling assumptions influence the environmental impacts of different WtE technologies and have been identified comprehensively in this study. These factors should therefore be focused on when considering potential areas of improvements throughout all stages of each WtE technology.

Fig. 1 .

 1 Fig. 1. System boundaries of LCA model.

Fig. 2 .

 2 Fig. 2. Configuration and mass flows in the four different WtE technologies. Data are adjusted to the functional unit of 1 tonne of MSW, values are expressed as kg.Letters "I" and "E" represent respectively "import" and "export".

Fig. 3 .

 3 Fig. 3. Characterized results of impact assessment for the treatment of 1 tonne of MSW using four different WtE technologies. Some impacts are scaled to fit the yaxis; their original values can be obtained by dividing the factor shown on the x-axis.

Fig. 4 .

 4 Fig. 4. Contribution analysis of different life cycle stages to the impacts from the four different WtE technologies. Only selected impact categories are shown in the figure, the impacts are estimated according to the CML 2001 method (updated in August 2016).

Fig. 5 .

 5 Fig. 5. Perturbation analysis results showing the most important parameters and their sensitivity ratios (SRs) in LCA results of the four different WtE technologies. Only SR greater than 0.2 and SR < -0.2 are presented.

Fig. 8 .

 8 Fig. 8. The effect of substituted options for electricity generation on the global warming potential (GWP) of the four different WtE technologies.

Fig. 9 .

 9 Fig. 9. The effect of using alternative functional unit on the environmental impacts of the four different WtE technologies: (a) with reference to 1 kwh of electricity generated; (b) with reference to 1 kwh of exergy in output products. Some impacts are scaled to fit the y-axis; their original values can be obtained by dividing the factor shown on the x-axis.

Table 1

 1 EU average Municipal solid waste composition assumed as reference for the LCA modelling.

	Waste composition	Content (wt%, as received basis)
	Organic waste	35
	Paper	20
	Plastics	11
	Textiles	4
	Glass	5
	Metals	3
	Other/inert waste a	22

Table 2

 2 Reference WtE plants considered in this study.

	Reference plants	110 French incineration plants [33,34]	Burgau, Germany [37,39]	Kymijärvi II, Finland [40,44]	A specified plant in Japan [27,32,45]
	Plant capacities (tonnes/year)	10,000-700,000	35,000	250,000	75,000
	Feedstock	Residual MSW	MSW, industrial waste, sewage sludge	Solid Refuse Fuels	MSW
	Type (supplier)	Moving grate	Rotary kiln	Circulating fluidized bed	Direct Melting System (shaft furnace)
	Technology	Incineration	Pyrolysis	Gasification	Gasification-melting
	Scenario	S1	S2	S3	S4

Table 3

 3 Life cycle inventory table for the four different WtE technologies, referred to the functional unit of 1 tonne of MSW.

			Unit	Incineration(S1)	Pyrolysis(S2)	Gasification(S3)	Gasification-melting (S4)
	Input streams
	Limestone as ancillary material	kg	-	-	-	70.20
	Quicklime as ancillary material	kg	-	-	-	16.00
	Coke as ancillary fuel Electricity for MSW pre-treatment	kg kwh	--	--a	-70.00	49.00 -
	Slaked lime for APC	kg	16.63	18.58	18.71	18.70
	Ammonia for APC	kg	0.52	0.52	0.52	0.52
	Active carbon for APC	kg	0.56	0.56	0.56	0.56
	Output solid residues to be treated
	Bottom ash, to be landfilled b	kg	277.43	-	102.73	-
	APC residues, to be stabilized followed by landfill	kg	48.09	64.72	125.93	64.90
	Direct emissions to air
	CO 2,fossil	c	kg	416.97	419.92	419.95	602.29
	CO		g	35.11	49.28	9.86	35.43
	HCl		g	31.07	25.13	4.93	21.15
	NH 3		g	24.64	24.64	24.64	28.57
	NO x PM d		g g	763.17 5.68	822.52 6.90	793.44 9.86	120.01 12.57
	SO 2		g	40.46	39.43	34.50	18.86
	Hg		g	3.14E-02	5.42E-02	4.93E-04	9.86E-02
	Dioxins		g	4.51E-08	4.93E-09	9.86E-09	4.97E-09
	Recovered streams (avoided burdens)
	Net electricity output	kwh	506.76	593.17	783.49	558.90
	Slag for road construction	kg	-	266.56	-	165.76
	Ferrous scrap	kg	15.46	10.76	7.98	-
	Aluminium scrap	kg	11.83	6.82	4.64	-
	Molten metals	kg	-	-	-	18.06

Acknowledgements

This project is supported by the French Centre National de la Recherche Scientifique (CNRS) and the Labex SOLSTICE (Agence Nationale de la Recherche, ANR).

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https:// doi.org/10.1016/j.enconman.2019.06.016.


Gérard Jaouen

Siden

Keywords: Estrogen receptor, 99m Tc radiolabelling, SPECT, tumor imaging, biodistribution, tumor

Synthesis and Biodistribution of 1-[2-(cyclopentadienyltricarbonyltechnetium-99m)-2oxo-ethoxy-phenyl]-1,2-di-(p-hydroxyphenyl)but-1-ene for tumor imaging

Tesnim Dallagi, Mouldi Saidi,

Synthesis and Biodistribution of 1-[2-(cyclopentadienyltricarbonyltechnetium-99m)-2oxo-ethoxy-phenyl

1. Introduction Some types of tumors are traditionally classified according to their hormone receptor status: Hormone-dependent tumors (Hormone receptor positive), and hormone-independent tumors (Hormone receptors negative). In the case of breast tumors, this designation comes from the fact that hormone-dependent cancer cells, whose proliferation is induced by estrogen, exhibit an accumulation of a specific intracellular receptor protein: the alpha form of the estrogen receptor (ERα). An adjuvant treatment with anti-estrogens or with aromatase inhibitors is used for patients with hormone-dependent breast cancer. These receptors serve as targets for endocrine therapies of these cancers [START_REF] Xu | 18F-labeled estradiol derivative for targeting estrogen receptorexpressing breast cancer[END_REF][START_REF] Fowler | Imaging Diagnostic and Therapeutic Targets: Steroid Receptors in Breast Cancer[END_REF][START_REF] Dixon | Exemestane and aromatase inhibitors in the management of advanced breast cancer[END_REF][START_REF] Winer | American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004[END_REF]. Knowledge of the receptor status can lead to more effective individualized treatment. But the receptors can also be used as targets for diagnostic imaging and radiotherapy. Diagnostic imaging can be achieved by administration of a suitably radiolabeled ligand that accumulates in the receptor-positive tumor cells where it can be detected and quantified by imaging. Such images can sometimes be used to predict whether hormone therapy might be effective or not [START_REF] Dehdashti | Positron emission tomographic assessment of "metabolic flare" to predict response of metabolic breast cancer to antiestrogen therapy[END_REF][START_REF] Oliveira | Steroid Receptor Ligands for Breast Cancer Targeting: An Insight into Their Potential Role As Pet Imaging Agents[END_REF][7][START_REF] Vanbrocklin | 18F]fluoro)estrogens: systematic investigation of a new series of fluorine-18-labeled estrogens as potential imaging agents for estrogen-receptor-positive breast tumors[END_REF]. Therefore, the development of such hormone receptor ligands for diagnostic imaging is a promising area of research.

Nuclear medicine imaging modalities, using specific targeting moieties, play a crucial role in the diagnosis, staging, and follow-up for patients with cancer. Radiotracer-based imaging approaches, such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET) could provide a non-invasive in vivo assessment providing information about tumor localization and progression [9]. Several radionuclides are used in nuclear medicine, including iodine-131, indium-111, thallium-201, fluorine-18, technetium-99m, gallium-67 and others [START_REF] Saha | Fundamentals of Nuclear Pharmacy[END_REF]. Technetium-99m ( 99m Tc) is one of the most common radiotracers for imaging. This isotope has suitable physical and chemical characteristics, including a physical half-life of 6.02 h and gamma emission of low energy (140 keV) with the added advantage of abundant availability in nuclear medicine laboratories and low cost [START_REF] De Barros | Radiolabeling of low molecular weight D-galactose-basedglycodendrimer with technetium-99 m and biodistribution studies[END_REF][START_REF] Monteiro | Technetium-99m radiolabeled paclitaxel as an imaging probe for breast cancer in vivo[END_REF][START_REF] Kong | Development of (99m)Tc-ECtyrosine for early detection of breast cancer tumor response to the anticancer drug melphalan[END_REF]. An interesting compound containing both 99m Tc and Pt, Pt-LQ-Tc ( LQ = mono((4-(3-(bis(quinolin-2-ylmethyl)amino)propylcarbamoyl)pyridinium-1-yl), has been designed in order to combine therapeutics and diagnosis in the same molecule [START_REF] Quental | Combining imaging and anticancer properties with new heterobimetallic Pt(II)/M(I) (M = Re, 99mTc) complexes[END_REF]. Diagnostic imaging of breast by positron emission tomography (PET) is well established [START_REF] Beauregard | Steroid receptor imaging in breast cancer[END_REF] and has been achieved using steroids labeled with fluorine-18 such as 16α-[ 18 F]fluoroestradiol (FES) [16]. Although a number of steroids labeled with bromine, fluorine and iodine radioisotopes have been prepared and studied [START_REF] Katzenellenbogen | 16 alpha-[77Br]bromo-11 beta-methoxyestradiol-17 beta: a gamma-emitting estrogen imaging agent with high uptake and retention by target organs[END_REF][START_REF] Landvatter | 2R*,3S*)-1-[125I]Iodo-2,3-bis(4-hydroxyphenyl)pentane ([125I]iodonorhexestrol) and (2R*,3S*)-1-[77Br]Bromo-2,3-bis(4-hydroxyphenyl)pentane ([77Br]bromonorhexestrol), two gamma-emitting estrogens that show receptor-mediated uptake by target tissues in vivo[END_REF][START_REF] Mcelvany | 16 alpha-[77Br]bromoestradiol: dosimetry and preliminary clinical studies[END_REF][START_REF] Pomper | 11β-Methoxy-, 11β-Ethyl-and 17α-Ethynyl-Substituted 16α-Fluoroestradiols: Receptor-Based Imaging Agents with Enhanced Uptake Efficiency and Selectivity[END_REF][START_REF] Seimbille | Synthesis of 16α-fluoro ICI 182,780 derivatives:powerful antiestrogens to image estrogen receptor densities in breast cancer by positron emission tomography[END_REF][START_REF] Van Brocklin | 18F]Fluoro)estrogens: systematic investigation of a new series of fluorine-18-labeled estrogens as potential imaging agents for estrogen-receptor-positive breast tumors[END_REF][START_REF] Oliveira | Steroid receptor ligands for breast cancer targeting: an insight into their potential role as PET imaging agents[END_REF][START_REF] Seimbille | 18Flabeled difluoroestradiols: preparation and preclinical evaluation as estrogen receptorbinding radiopharmaceuticals[END_REF][25], especially in terms of their potential for selective radiotherapy, their use in imaging studies, particularly in humans, has been more limited. While most of these agents were based on steroidal estrogens, a few investigations were focused on nonsteroidal estrogens or antiestrogens including selective ER modulators (SERMs) [START_REF] Dixon | Exemestane and aromatase inhibitors in the management of advanced breast cancer[END_REF].

In 1996, Jaouen and coworkers coupled ferrocene to the biovector hydroxytamoxifen to create a new class of compounds, called ferrocifens [START_REF] Top | Ferrocenyl hydroxytamoxifen: a prototype for a new range of oestradiol receptor site-directed cytotoxics[END_REF]. These compounds were initially designed to combine the antiestrogenic properties of tamoxifen with a potential cytotoxic effect of ferrocene to possibly obtain new therapeutic advantages [START_REF] Jaouen | The first organometallic antioestrogens and their antiproliferative effects[END_REF][START_REF] Top | Synthesis, biochemical properties and molecular modelling studies of organometallic specific estrogen receptor modulators (SERMs), the ferrocifens and hydroxyferrocifens: evidence for an antiproliferative effect of hydroxyferrocifens on both hormone-dependent and hormone-independent breast cancer cell lines[END_REF]. In an effort to develop this class of compounds, 1-(2-ferrocenyl-2-oxoethoxyphenyl)-1,2-bis-(4hydroxyphenyl)but-1-ene, 1, was synthesized (Chart 1) [START_REF] Nguyen | Synthesis and structure-activity relationships of ferrocenyl tamoxifen derivatives with modified side chains[END_REF]. This type of ferrocenyl compound is suitable for use as a precursor in the synthesis of the technetium analog, 2 (Chart 1), by performing an organometallic exchange reaction developed for steroids by Wenzel [START_REF] Wenzel | Tc-99m markierte Östradiol-derivate synthese, organverteilung und tumor-affinität[END_REF] and Katzenellenbogen [START_REF] Spradau | Synthesis and biological evaluation of Tc-99mcyclopentadienyltricarbonyltechnetium-labeled octreotide[END_REF][START_REF] Minutolo | A Convenient Three-Component Synthesis of Substituted Cyclopentadienyl Tricarbonyl Rhenium Complexes[END_REF].

Chart 1. Ferrocenyl, manganese and 99m Tc derivatives.

In 2001, Alberto found an efficient method to generate aqua-ion [ 99m Tc(CO)3(H2O)3] + [START_REF] Alberto | Synthesis and Properties of Boranocarbonate: A Convenient in Situ CO Source for the Aqueous Preparation of [99mTc(OH2)3(CO)3]+[END_REF].

He demonstrated later that the cyclopentadienyltricarbonyltechnetium compound could be conveniently prepared from a reaction between [ 99m Tc(CO)3(H2O)3] + and cyclopentadienide derivatives [34][START_REF] Alberto | New organometallic Technetium Complexes for radiopharmaceutical imaging[END_REF][START_REF] Can | Cp-R)M(CO)3] (M=Re or 99mTc) Arylsulfonamide, arylsulfamide, and arylsulfamate conjugates for selective targeting of human carbonic anhydrase IX[END_REF]. 2 was first obtained from the reaction of 1 with [ 99m Tc(CO)3(H2O)3] + in DMSO/water at 120°C [37]. The best yield obtained for 2 was 70%, which is slightly too low to allow the use of this approach for biodistribution study. We have now found good conditions for the double ligand transfer reaction involving 1, [ 99m TcO4] -and Mn(CO)5Br to produce 2 in 95% yield. For identification of the technetium compound, a manganese or rhenium analog was used for comparison using the HPLC technique [START_REF] Masi | Direct synthesis of tricarbonyl(cyclopentadienyl)rhenium and tricarbonyl(cyclopentadienyl)technetium units from ferrocenyl moieties -Preparation of 17 alpha-ethynylestradiol derivatives bearing a tricarbonyl(cyclopentadienyl)technetium group[END_REF][START_REF] Dallagi | Synthesis and antiproliferative evaluation of ferrocenyl and cymantrenyl triaryl butene on breast cancer cells. Biodistribution study of the corresponding technetium-99m tamoxifen conjugate[END_REF]. Therefore, 1-[4-

(2-(cyclopentadienyltricarbonylmanganese)-2-oxo-ethoxy)phenyl]-1,2-di(p-hydroxyphenyl)-
but-1-ene, 3, was also prepared [START_REF] Dallagi | Synthesis and antiproliferative activity of (Z + E)-1-[4-(2-(cyclopentadienyltricarbonylmanganese)-2-oxo-ethoxy)phenyl]-1,2-di(p -hydroxyphenyl)-but-1-ene against breast cancer cells[END_REF]. In the present study, we report the synthesis of 2 and the determination of in vitro radiochemical stability. In addition, blood circulation time was evaluated. A biodistribution study was also performed to demonstrate the feasibility of using 2 as a potential agent for imaging estrogen receptors (ERs) in breast tumor.

Experimental

The synthesis of the ferrocenyl complex, 1 [START_REF] Nguyen | Synthesis and structure-activity relationships of ferrocenyl tamoxifen derivatives with modified side chains[END_REF] and the cyclopentadienyltricarbonylmanganese derivative, 3 [START_REF] Dallagi | Synthesis and antiproliferative evaluation of ferrocenyl and cymantrenyl triaryl butene on breast cancer cells. Biodistribution study of the corresponding technetium-99m tamoxifen conjugate[END_REF] have been previously published.

2.1. 1-[2-(cyclopentadienyltricarbonyltechnetium-99)-2-oxo-ethoxy-phenyl]-1.2-di-(p- hydroxyphenyl)but-1-ene, 2
1 (1 mg) and Mn(CO)5Br (1 mg) were dissolved in 150 µL of dimethylformamide in a 10 mL glass tube and 150 µL [ 99m TcO4] -in saline was added. The vial was sealed and purged with nitrogen for 10 min and heated in an oil bath at 150 ºC for 1 h. The mixture was purified by chromatography on a silica gel plate (TLC) (diethyl ether/petroleum ether 8/2) to give 2.

Radio-TLC (diethyl ether) gave a peak with an Rf = 0.8 (yield 90 %). HPLC retention time =

22.73 min. The solution was purified from 99m TcO2 using a 0.22 mm syringe filter, as previously described by Fernandes et al [START_REF] Fernandes | Technetium-99 m radiolabeled paclitaxel as an imaging probe for breast cancer in vivo[END_REF].

Biological pH stability study.

Purified 2 (100 µL. 60 µCi) was added to potassium phosphate buffer (900 mL, 0.1M) at pH 7.4. The vial was sealed and incubated at 37.0 ºC for the duration of study. The solution was examined by radio-HPLC at 30 min. 1 h, 2 h, 3 h and 24 h during incubation to determine the effective stability of the compound.

In vitro stability study.

An in vitro stability study was carried out in isolated heparinized whole rat blood (mature female Wistar rats). The whole blood (5 mL) was incubated with 100 µCi of 2 in 100 µL ethanol for 30 min, 1 h, 2 h, 3h and 24 h at 37.0 ºC. A sample of blood (1 mL) was taken from the solution each time. The sample was centrifuged at 5000 rpm for 5 min to separate plasma and cellular fractions and individual fractions were counted in a well counter. The plasma was then treated with CH3CN (1 mL) and centrifuged as before and the supernatant was separated from the precipitated debris. The fractions were again counted with the bulk of activity residing in the plasma supernatant. The radioactive species in the supernatant were analysed by radio-HPLC.

Kinetic study

The kinetic study was carried out according to the relevant national regulation using mature

(5-6 weeks old) female Wistar rats weighing between 180 and 200 g. Purified 2 was dissolved in 15% ethanol/saline buffer and injected via the tail vein. The dose employed was 80 µCi per animal (in 300 mL volume). At the specified time points post-injection of 2, blood samples were collected by heart puncture. The injected dose (ID) was calculated by comparison with dose standards prepared from the injected solution at appropriate counting rates. The data were expressed as percentage of ID per gram of tissue (% ID/g of blood). The biological halflife of compound 2 was determined using the following formula:

Tb = Tp x Teff / Tp -Teff; Teff = 0.693/Ke; Ke = log (C1/C2) / t2 -t1; Ke = elimination constant determined from curve.

In vivo biodistribution.

The biodistribution studies were carried out according to the relevant national regulation using mature (5-6 weeks old) female Wistar rats weighing between 180 and 200 g. Purified 2

was dissolved in 15% ethanol/saline buffer and injected via the tail vein under slight ether anesthesia. The dose employed was 80 µCi per animal (in 300 mL volume). and one set of animals was co-injected with radiotracer together with a blocking dose (15 mg) of estradiol.

At the specified time points post-injection of 2, groups of three animals each were sacrificed by heart puncture; tissues of interest were removed and weighed; and radioactivity was counted. The injected dose (ID) was calculated by comparison with dose standards prepared from the injected solution at appropriate counting rates. The data were expressed as percentage of ID per gram of tissue (% ID/g of tissue). For each animal group, the data were averaged and standard deviation was calculated. Data were analysed by multifactorial analysis of variance (ANOVA. SPSS 12.0 for Windows) and significant differences among treatments were considered using Student's t test at the P < 0.05 level.

Results and discussion

Synthesis

Intensive development of nuclear medicine in the field of cancer diagnosis and therapy is currently taking place. The most important diagnostic and therapeutic radiopharmaceuticals, which selectively distribute within given tissues or organs, are formed by coordination compounds with a diagnostic or therapeutic radiometal firmly attached to a selected biologically active molecule. Among diagnostic radionuclides technetium-99m (T1/2 = 6 h, Eɣ = 140 keV) is most commonly used for SPECT applications due to its favorable physical properties, ready availability from the 99 Mo-99m Tc generator and relatively low cost [START_REF] Cutler | Radiometals for combined imaging and therapy[END_REF].

The synthesis of the ferrocenyl derivative 1 was published in the literature [START_REF] Nguyen | Synthesis and structure-activity relationships of ferrocenyl tamoxifen derivatives with modified side chains[END_REF]. The IC50 values of 11.3 µM and 7.8 µM were found respectively against hormone-dependent breast cancer cells (MCF-7) and against prostate cancer cells PC3. Its relative binding affinity (RBA) value for the alpha form of the estrogen receptor is 14%.

Cyclopentadienyltricarbonylmanganese compound 3 was prepared according to the literature procedure [START_REF] Dallagi | Synthesis and antiproliferative activity of (Z + E)-1-[4-(2-(cyclopentadienyltricarbonylmanganese)-2-oxo-ethoxy)phenyl]-1,2-di(p -hydroxyphenyl)-but-1-ene against breast cancer cells[END_REF].

Scheme 1 shows the synthesis of cyclopentadienyltricarbonyltechnetium compound 2.

Scheme 1. synthesis of cyclopentadienyltricarbonyltechnetium compound 2

Heating the mixture of 1 with [ 99m TcO4] -and Mn(CO)5Br in dimethylformamide in a sealed tube at 150°C for 90 min resulted in formation of technetium compound 2 in 95% yield after purification by TLC chromatography. The technetium compound, 2, was identified by comparison of its retention time to that of manganese analog 3 (Figure 1).

The radiolabeling protocol to obtain compound 2 was successfully optimized to achieve high yields. According to the American Pharmacopoeia [43], radiopharmaceutical preparations are suitable for in vivo administration if their radioactive impurities do not exceed 10%. Use of the optimized protocol described in this study resulted in the detection of

Biochemical studies

The in vitro stability study was carried out in isolated whole rat blood following the procedure reported in the literature [START_REF] Dallagi | Synthesis and antiproliferative evaluation of ferrocenyl and cymantrenyl triaryl butene on breast cancer cells. Biodistribution study of the corresponding technetium-99m tamoxifen conjugate[END_REF][START_REF] Dallagi | Synthesis and antiproliferative activity of (Z + E)-1-[4-(2-(cyclopentadienyltricarbonylmanganese)-2-oxo-ethoxy)phenyl]-1,2-di(p -hydroxyphenyl)-but-1-ene against breast cancer cells[END_REF][START_REF] Parent | Synthesis and biological evaluation of a nonsteroidal bromine-76-labeled androgen receptor ligand 3-[76Br] bromo-hydroxyflutamide[END_REF]. Around 93% of the radioactivity was separated into supernatant from the pellet over the period of 3 h, indicating little binding to cells or cellular proteins in the blood. According to the radio-HPLC analysis of the supernatant. 2 was the only radioactive species observed during 30 min of incubation.

Compound 2 was also incubated with a potassium phosphate buffer at 37°C for 22 h; the same stability results were found (figure 2). Radiolabeling stability is a mandatory characteristic for radiopharmaceutical platforms. In the event that metal detachment occurs, biodistribution and images will no longer be reliable and may lead to wrong interpretations [START_REF] Can | Cp-R)M(CO)3] (M=Re or 99mTc) Arylsulfonamide, arylsulfamide, and arylsulfamate conjugates for selective targeting of human carbonic anhydrase IX[END_REF][37]. 2 showed high stability in vitro (over 95%) throughout the experiment (Figure 2).

The kinetic study was undertaken on female Wistar rats. A solution of purified 2 in 15% ethanol/saline buffer was injected via the tail vein. Blood samples were collected by heart puncture at 30 min, 1 h, 2 h, 3 h et 24 h post injection for concentration determination.

Figure 3 shows that the plasma activity increased significantly during first 30 min before a fast decrease within 5 h. After that time, a slow decrease was observed until 20 h. Using this last curve section for the half-live determination, a value of 14.68 h was found for the half-life of 2.

Figure 3 . In vivo disappearance of compound 2 in mature female rats.

Comparing to the cyclopentadienyltricarbonyltechnetium-99m 4 (Chart 2), published before in literature [START_REF] Dallagi | Synthesis and antiproliferative evaluation of ferrocenyl and cymantrenyl triaryl butene on breast cancer cells. Biodistribution study of the corresponding technetium-99m tamoxifen conjugate[END_REF], 2 is more stable (14.68 h versus 5.52 h)

Chart 2 Cyclopentadienyltricarbonyltechnetium-99m 4
Long circulation time is an important feature for radiopharmaceuticals since a large number of passages through the targeted areas might favor radiotracer accumulation leading to better target/non-target ratios. For imaging purposes, a stability of compound with a halflife ranging from 4 to 6 h is suitable to achieve a reasonable signal-to-noise ratio [START_REF] Monteiro | Technetium-99m radiolabeled paclitaxel as an imaging probe for breast cancer in vivo[END_REF].

A biodistribution study was thus performed to demonstrate the feasibility of 2 as a radiotracer for breast cancer. Purified 2 was reconstituted in 15% ethanol-saline and injected into mature female Wistar rats (180 to 200 g) via the tail vein. The dose of 2 employed was 80 µCi/animal. Animals were sacrificed at 15 min, 1 h, 2 h, 3 h, 6 h, 18 h and 24 h post-injection.

Table 1 shows the uptake of 2 in selected tissues of rats. The uptake values were calculated as a percent injected dose per gram of tissue (% ID/g).

---------------------------Table 1 ---------------------------At 15 min post injection, the uptake by uterus is similar to ovaries and in the same range as for muscle and bone. Interestingly, the ovaries/muscle and uterus/muscle ratios are 2.01± 0.01 and 2±0.02, respectively, thus opening the possibility of imaging of these organs.

At 2 h post-injection point, there is an uptake by ovaries with 0.66 ± 0.07 % ID/g.

Apart from the high uptake by the liver and lung (9.87 ± 1.68 and 21.86 ± 1.70 % ID/g, respectively), the uptake of kidney, spleen and heart is higher than that of ovaries. The ovaries/muscle and ovaries/blood ratios are 6.11 and 1.94 respectively. At 6 h post-injection, uptake in the ovaries was reduced to 0.183 ± 0.015% ID/g; while up to 75 % of the radioactivity in liver and lung was washed out. At 24 h post injection, all tissue activities were reduced with highest activity in the liver. We note that the biodistribution shows a significant uptake in the liver, lung and spleen due to the importance of these routes for excretion. To determine whether the uptake was mediated by a high affinity, limited-capacity system, a blocking study was carried out by co-injection of 80 µCi of 2 together with 18 µg/g estradiol to fully occupy the ER sites. The results are shown in Table 2. Uptake in ER-rich target tissues (uterus and ovaries) was reduced to 0.11 ± 0.01 and 0.24 ± 0.01, respectively.

This result indicates that the uptake of 2 in the ovaries is mediated by binding to ER. No obvious differences in activity levels were observed in blood, liver, lung and spleen between blocked and nonblocked animals. [START_REF] Dallagi | Synthesis and antiproliferative evaluation of ferrocenyl and cymantrenyl triaryl butene on breast cancer cells. Biodistribution study of the corresponding technetium-99m tamoxifen conjugate[END_REF], [45].

Table 3 shows the biodistribution of compound 2 and 4 in mature female rats. A compared to 4, 2 attains a maximum uptake at 2h while the uptake of 4 starts to decrease from 15 min. The uptakes of 2 by ovaries and by uterus are similar, while the uptake of 4 by ovaries is much higher than that by uterus. Figure 4 shows uterus to muscle ratios and ovaries to muscle ratios of 2 and 4. 4 has higher uterus to muscle ratios than that of 3. For ovaries, 4 still has better ratio value than 2 at 1h but lower at 15 min. The difference between the uptake of 2 and 4 may be due to the fact that 4 has good affinity for ER in ER rich tissue (uterus and ovaries) [START_REF] Dallagi | Synthesis and antiproliferative evaluation of ferrocenyl and cymantrenyl triaryl butene on breast cancer cells. Biodistribution study of the corresponding technetium-99m tamoxifen conjugate[END_REF].

Conclusion

We have developed suitable conditions for the synthesis of 99m Tc compound 2. It was obtained in good yields (90%). Tissue distribution showed a significant selective uptake by the ovaries and a low level of activity in muscle. The fact that the ovaries/muscle uptake ratio shows a significant reduction when the receptor is blocked by co-injection of large excess of estradiol means that this uptake is ER mediated. Further studies, involving the metabolic stability of compound 2 in in vivo tumor model experiments, are currently underway. Table 1. Tissue biodistribution of compound 2 in mature female rats (%ID/g of tissue)

Table 2. Tissue biodistribution of 2 in mature female rats: blocking study.

Table 3. Tissue biodistribution of compound 2 and 4 in mature female rats percent injected dose/g of tissue ±s.d (%ID/g of tissue).

Highlights:

Ferrocenyl butene compound was prepared for its use as a precursor of Tc analog. Using metal exchange reaction, ferrocenyl compound was transformed to 99m Tc analog in 90% yield. Biodistribution of the Tc compound was studied in rats. Uptake by ovaries was mediated by hormone receptors.

  hydroxyphenyl)but-1-ene for tumor imaging Tesnim Dallagi, a * Mouldi Saidi, a Gérard Jaouen, b,c Siden Top c* a) Laboratoire de biotechnologies et technologies nucléaires. Centre National des Sciences et Technologies Nucléaires. Technopôle de Sidi Thabet. 2020 Sidi Thabet Tunisie b) PSL, Chimie ParisTech, 11 rue Pierre et Marie Curie, F-75005 Paris, France c) Sorbonne Université, UPMC Univ Paris 6, UMR 8232 CNRS, IPCM, place Jussieu, F-75005 Paris, France Correspondence:

Figure 1 .

 1 Figure 1. (a) UV-HPLC (254 nm) chromatogram of 3 and (b) Radio-HPLC chromatogram of 2.The technetium compound, 2, was identified by comparison of its retention time to

Figure 2 .

 2 Figure 2. In vitro stability of 2 as a function of time in the presence of saline solution (Series

Figure 4 .

 4 Figure 4. Uterus to muscle ratios (a) and ovaries-to-muscle ratios (b) determined by tissue biodistribution at 2 h post injection of compound 2 and 4 [45] respectively.

Chart 2 Cyclopentadienyltricarbonyltechnetium-99m 4 Scheme 1 . synthesis of cyclopentadienyltricarbonyltechnetium compound 2 Figure 1 .

 24121 Scheme 1. synthesis of cyclopentadienyltricarbonyltechnetium compound 2

Figure 2 .

 2 Figure 2. In vitro stability of 2 as a function of time in the presence of saline solution (Series

Figure 3 .

 3 Figure 3. In vivo disappearance of compound 2 in mature female rats.

Figure 4 .

 4 Figure 4. Uterus to muscle ratios (a) and ovaries-to-muscle ratios (b) determined by tissue biodistribution at 2 h post injection of compound 2 and 4 [45] respectively.

Table 2 .

 2 Tissue biodistribution of 2 in mature female rats: blocking study.

		Percent injected dose/gram ± S.D. (n=3)
		2h	2h (Block)
	blood	0.33	±0.06
	liver	9.87	±1.68
	bone	0.14	±0.03
	Muscle	0.11	±0.04
	lung	21.86	±0.70
	Uterus	0.28	±0.06
	ovaries	0.61	±0.08
	Kidney	1.47	±0.24
	spleen	8.86	±0.75
	heart	0.37	±0.09
	Uterus/Muscle	3.02	±0.86
	Uterus/blood	0.89	±0.27
	Ovaries/Muscle	6.11	±0.32
	Ovaries/blood	1.94	±0.65
	*2 h block indicates co-administration of 15 µg estradiol.

Table 3 .

 3 Tissue biodistribution of compound 2 and 4 in mature female rats percent injected dose/g of tissue ±s.d (%ID/g of tissue).

		Compound 2	4*
		Ovaries	Uterus	Ovaries	Uterus
	15 min	0.199 ±0.002	0.197 ±0.04	1.76 ±0.10	0.44 ±0.15
	1 h	0.27 ±0.060	0.236 ±0.14	0.42 ±0.03	0.2 ±0.05
	2 h	0.61 ±0.070	0.283 ±0.05	0.45 ±0.08	0.2 ±0.02
	3 h	0.56 ±0.013	0.17 ±0.01	0.13 ±0.01	0.07 ±0.02
	6 h	0.183 ±0.01	0.01 ±0.010	0.12 ±0.02	0.04 ±0.01
	18 h	0.021 ±0.000	0.045 ±0.04	0.06 ±0.01	0.04 ±0.01

Table 1 .

 1 Tissue biodistribution of compound 2 in mature female rats (%ID/g of tissue) Ferrocenyl, manganese and 99m Tc derivatives.

		Percent injected dose/gram±S.D. (n=3)
		15 min	1 h	2 h	3 h	6 h	18 h	24 h
	Blood	0.46 ±0.05	0.33 ±0.11	0.39 ±0.05	0.31 ±0.01	0.13 ±0.00	0.03 ±0.01	0.02 ±0.02
	Liver	2.43 ±0.64	7.78 ±0.63	9.87 ±1.68	10.52 ±0.89	1.89 ±0.720	0.24 ±0.04	0.580 ±0.07
	bone	0.23 ±0.09	0.12 ±0.03	0.14 ±0.031	0.20 ±0.05	0.06 ±0.015 0.016 ±0.0	0.022 ±0.00
	Muscle	0.09 ±0.00	0.12 ±0.02	0.11 ±0.04	0.17 ±0.06	0.034 ±0.003 0.006 ±0.00	0.007 ±0.00
	Lung	7.69 ±0.89	6.62 ±0.25	21.86 ±0.70	24.81 ±0.60	6.20 ±0.943 1.067 ±0.30	1.143 ±0.022
	Uterus	0.19 ±0.04	0.23 ±0.14	0.28 ±0.05	0.17 ±0.01	0.1 ±0.01	0.045 ±0.04	0.033 ±0.04
	Ovaries	0.19 ±0.00	0.27 ±0.06	0.61 ±0.07	0.56 ±0.013	0.18 ±0.01	0.021 ±0.00	0.036 ±0.02
	kidney	0.43 ±0.02	0.47 ±0.18	1.47 ±0.023	2.03 ±0.045	1.13 ±0.038 0.440 ±0.016 0.340 ±0.016
	Spleen	1.32 ±0.23	6.49 ±0.43	8.85 ±0.75	4.84 ±0.09	0.28 ±0.09	0.044 ±0.01	0.081 ±0.01
	Heart	0.22 ±0.02	0.21 ±0.06	0.36 ±0.08	0.3 ±0.08	0.15 ±0.01	0.025 ±0.00	0.031 ±0.01

Acknowledgements.

We thank the Ministère de l'Enseignement Supérieur et de la Recherche de Tunisie, the Centre National des Sciences et Technologies Nucléaires de Tunisie for financial support.