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
{"title":"一种靶向成纤维细胞活化蛋白（FAP）的新型PET示踪剂[68Ga]Ga-AAZTA-FAPI-46的临床前评估。","authors":"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","doi":"10.1186/s41181-025-00375-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":"51"},"PeriodicalIF":4.4000,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325145/pdf/","citationCount":"0","resultStr":"{\"title\":\"Preclinical evaluation of [<sup>68</sup>Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP).\",\"authors\":\"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\",\"doi\":\"10.1186/s41181-025-00375-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":534,\"journal\":{\"name\":\"EJNMMI Radiopharmacy and Chemistry\",\"volume\":\"10 1\",\"pages\":\"51\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2025-08-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325145/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EJNMMI Radiopharmacy and Chemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1186/s41181-025-00375-2\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, INORGANIC & NUCLEAR\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EJNMMI Radiopharmacy and Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s41181-025-00375-2","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, INORGANIC & NUCLEAR","Score":null,"Total":0}
引用次数: 0
摘要
背景：本研究的目的是证明AAZTA螯合剂与fapi -46衍生的FAP抑制剂结合并标记为镓-68作为潜在的PET示踪剂的适用性。结果：镓-68在室温下具有较高的放射化学产率。该示踪剂在不同介质中均表现稳定，在体外和体内均与fap蛋白具有特异性结合，具有合适的生物分布和清除能力。在4t1荷瘤小鼠中发现了高的肿瘤摄取（1.01±0.12 SUV 35 min p.i.），阻断实验显示了高的靶标特异性。结论：用FAPI-46片段上的AAZTA配体取代DOTA螯合剂可以在室温下对PET示踪剂进行快速放射性标记，而不影响生物分布特性，如清除率和fap介导的肿瘤吸收，反而扩大了示踪剂的适用性。
Preclinical evaluation of [68Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP).
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.
![Preclinical evaluation of [<sup>68</sup>Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP).](https://img.booksci.cn/booksciimg/2025-8/2025081678252452723630259906996.jpg)
![Preclinical evaluation of [<sup>68</sup>Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP).](https://img.booksci.cn/booksciimg/2025-8/2025081678254571806556530301177.jpg)
![Preclinical evaluation of [<sup>68</sup>Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP).](https://img.booksci.cn/booksciimg/2025-8/2025081678288253726588443664672.jpg)
![Preclinical evaluation of [<sup>68</sup>Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP).](https://img.booksci.cn/booksciimg/2025-8/2025081978252290592486704203942.jpg)
![Preclinical evaluation of [<sup>68</sup>Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP).](https://img.booksci.cn/booksciimg/2025-8/2025081978256435021249213171857.jpg)
![Preclinical evaluation of [<sup>68</sup>Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP).](https://img.booksci.cn/booksciimg/2025-8/202508197829725749383225236617.jpg)
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
