Preclinical evaluation of [68Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP)
Abstract Background The aim of this work was to demonstrate the suitability of AAZTA chelator conjugated to a FAPI-46-derived FAP inhibitor and labelled with gallium-68 as a potential PET tracer. Results Gallium-68 radiolabelling was achieved with high radiochemical yield at room temperature. The ne...
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SpringerOpen
2025-08-01
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| Series: | EJNMMI Radiopharmacy and Chemistry |
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| Online Access: | https://doi.org/10.1186/s41181-025-00375-2 |
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| author | Rebecca Rizzo Paolo Rainone Rachele Stefania Sara Belloli Silvia Valtorta Angela Coliva Marco Maspero Lidia Avalle Martina Capozza Rosa Maria Moresco Calogero D’Alessandria Enzo Terreno |
| author_facet | Rebecca Rizzo Paolo Rainone Rachele Stefania Sara Belloli Silvia Valtorta Angela Coliva Marco Maspero Lidia Avalle Martina Capozza Rosa Maria Moresco Calogero D’Alessandria Enzo Terreno |
| author_sort | Rebecca Rizzo |
| collection | DOAJ |
| description | Abstract Background The aim of this work was to demonstrate the suitability of AAZTA chelator conjugated to a FAPI-46-derived FAP inhibitor and labelled with gallium-68 as a potential PET tracer. Results Gallium-68 radiolabelling was achieved with high radiochemical yield at room temperature. The new tracer was stable in different media, showing specific binding to FAP-protein both in vitro and in vivo, and a suitable biodistribution and clearance. High tumor uptake of the tracer (1.01 ± 0.12 SUV 35 min p.i.) was found in 4T1-tumor bearing mice, and blocking experiments demonstrated the high target specificity. Conclusion The substitution of the DOTA chelator with the AAZTA ligand on FAPI-46 moiety allowed a fast radiolabelling at room temperature of the PET tracer without influencing the biodistribution properties, such as clearance and FAP-mediated tumor uptake, but rather expanding the tracer applicability. |
| format | Article |
| id | doaj-art-9480bd55d0394618a8435f116d57ef63 |
| institution | Kabale University |
| issn | 2365-421X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | EJNMMI Radiopharmacy and Chemistry |
| spelling | doaj-art-9480bd55d0394618a8435f116d57ef632025-08-20T04:03:12ZengSpringerOpenEJNMMI Radiopharmacy and Chemistry2365-421X2025-08-0110111310.1186/s41181-025-00375-2Preclinical evaluation of [68Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP)Rebecca Rizzo0Paolo Rainone1Rachele Stefania2Sara Belloli3Silvia Valtorta4Angela Coliva5Marco Maspero6Lidia Avalle7Martina Capozza8Rosa Maria Moresco9Calogero D’Alessandria10Enzo Terreno11Center for Biotechnology and Translational Medicine, University of TurinNuclear Medicine and PET Cyclotron Unit, IRCCS Ospedale San RaffaeleDISIT, University of Eastern PiedmontNuclear Medicine and PET Cyclotron Unit, IRCCS Ospedale San RaffaeleNuclear Medicine and PET Cyclotron Unit, IRCCS Ospedale San RaffaeleNuclear Medicine and PET Cyclotron Unit, IRCCS Ospedale San RaffaeleNuclear Medicine and PET Cyclotron Unit, IRCCS Ospedale San RaffaeleDISIT, University of Eastern PiedmontCenter for Biotechnology and Translational Medicine, University of TurinNuclear Medicine and PET Cyclotron Unit, IRCCS Ospedale San RaffaeleDepartment of Nuclear Medicine, TUM University Hospital rechts der IsarCenter for Biotechnology and Translational Medicine, University of TurinAbstract Background The aim of this work was to demonstrate the suitability of AAZTA chelator conjugated to a FAPI-46-derived FAP inhibitor and labelled with gallium-68 as a potential PET tracer. Results Gallium-68 radiolabelling was achieved with high radiochemical yield at room temperature. The new tracer was stable in different media, showing specific binding to FAP-protein both in vitro and in vivo, and a suitable biodistribution and clearance. High tumor uptake of the tracer (1.01 ± 0.12 SUV 35 min p.i.) was found in 4T1-tumor bearing mice, and blocking experiments demonstrated the high target specificity. Conclusion The substitution of the DOTA chelator with the AAZTA ligand on FAPI-46 moiety allowed a fast radiolabelling at room temperature of the PET tracer without influencing the biodistribution properties, such as clearance and FAP-mediated tumor uptake, but rather expanding the tracer applicability.https://doi.org/10.1186/s41181-025-00375-2AAZTAFAPPETFAPI-46GALLIUM-68 |
| spellingShingle | Rebecca Rizzo Paolo Rainone Rachele Stefania Sara Belloli Silvia Valtorta Angela Coliva Marco Maspero Lidia Avalle Martina Capozza Rosa Maria Moresco Calogero D’Alessandria Enzo Terreno Preclinical evaluation of [68Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP) EJNMMI Radiopharmacy and Chemistry AAZTA FAP PET FAPI-46 GALLIUM-68 |
| title | Preclinical evaluation of [68Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP) |
| title_full | Preclinical evaluation of [68Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP) |
| title_fullStr | Preclinical evaluation of [68Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP) |
| title_full_unstemmed | Preclinical evaluation of [68Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP) |
| title_short | Preclinical evaluation of [68Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP) |
| title_sort | preclinical evaluation of 68ga ga aazta fapi 46 a novel pet tracer for targeting fibroblast activation protein fap |
| topic | AAZTA FAP PET FAPI-46 GALLIUM-68 |
| url | https://doi.org/10.1186/s41181-025-00375-2 |
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