Liang Zhao, Yizhen Pang, Daqiang Xu, Jianhao Chen, Shan Yu, Dan Ruan, Lingyu Yu, Zhenyu Wu, Guoqiang Su, Hua Wu, Lin Ai, Long Sun, Di Fan, Haojun Chen
{"title":"针对FAP的新型双模pet/荧光探针用于准确划定肿瘤边缘的临床前和临床试验评估。","authors":"Liang Zhao, Yizhen Pang, Daqiang Xu, Jianhao Chen, Shan Yu, Dan Ruan, Lingyu Yu, Zhenyu Wu, Guoqiang Su, Hua Wu, Lin Ai, Long Sun, Di Fan, Haojun Chen","doi":"10.1007/s00259-025-07512-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Accurate delineation of tumor margins and maximal safe resection are critical for successful curative oncologic surgery. However, fibroblast activation protein (FAP)-targeted probes suitable for fluorescence imaging remain limited. Here, we developed novel FAP-targeted fluorescent probes to accurately delineate tumor margins and enable rapid intraoperative identification of tumor boundaries in resected specimens.</p><p><strong>Methods: </strong>DOTA chelator for radiolabelling with gallium-68 was incorporated into dual-modality FAP-targeted probes synthesised by conjugating FAP-2286 and 3BP-3940 with the near-infrared (NIR) fluorophore IRDye800CW. These probes were evaluated both in vitro and in vivo using HEK293T-FAP cells stably expressing FAP and xenograft mouse models. Positron emission tomography (PET) and (NIR-II) fluorescence imaging assessed the specificity and ability of probes to delineate tumor margins. For clinical validation, resected lung tissue was incubated ex vivo with the probes. Tumor regions and margins were identified using fluorescence imaging and subsequently validated by haematoxylin and eosin (H&E) staining and FAP immunohistochemistry.</p><p><strong>Results: </strong>Both IRDye800CW-FAP-2286 and IRDye800CW-3BP-3940 exhibited high affinity for FAP-positive cells in vitro. PET imaging revealed high tumor specificity for both probes in vivo. In vivo and ex vivo NIR-II fluorescence imaging enabled accurate visualisation of tumor margins, with IRDye800CW-3BP-3940 exhibiting superior performance compared with IRDye800CW-FAP-2286. In the clinical specimen, IRDye800CW-3BP-3940 successfully delineated tumor regions with strong concordance to histopathological findings.</p><p><strong>Conclusion: </strong>We developed and validated a novel dual-modality molecular probe, IRDye800CW-3BP-3940, which integrated PET and NIR fluorescence imaging capabilities. This probe enabled highly specific detection of FAP-positive tumors and precise delineation of tumor margins in resected specimens.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":""},"PeriodicalIF":7.6000,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Preclinical and pilot clinical evaluation of novel dual-modality pet/fluorescence probes targeting FAP for accurate tumor margin delineation.\",\"authors\":\"Liang Zhao, Yizhen Pang, Daqiang Xu, Jianhao Chen, Shan Yu, Dan Ruan, Lingyu Yu, Zhenyu Wu, Guoqiang Su, Hua Wu, Lin Ai, Long Sun, Di Fan, Haojun Chen\",\"doi\":\"10.1007/s00259-025-07512-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Accurate delineation of tumor margins and maximal safe resection are critical for successful curative oncologic surgery. However, fibroblast activation protein (FAP)-targeted probes suitable for fluorescence imaging remain limited. Here, we developed novel FAP-targeted fluorescent probes to accurately delineate tumor margins and enable rapid intraoperative identification of tumor boundaries in resected specimens.</p><p><strong>Methods: </strong>DOTA chelator for radiolabelling with gallium-68 was incorporated into dual-modality FAP-targeted probes synthesised by conjugating FAP-2286 and 3BP-3940 with the near-infrared (NIR) fluorophore IRDye800CW. These probes were evaluated both in vitro and in vivo using HEK293T-FAP cells stably expressing FAP and xenograft mouse models. Positron emission tomography (PET) and (NIR-II) fluorescence imaging assessed the specificity and ability of probes to delineate tumor margins. For clinical validation, resected lung tissue was incubated ex vivo with the probes. Tumor regions and margins were identified using fluorescence imaging and subsequently validated by haematoxylin and eosin (H&E) staining and FAP immunohistochemistry.</p><p><strong>Results: </strong>Both IRDye800CW-FAP-2286 and IRDye800CW-3BP-3940 exhibited high affinity for FAP-positive cells in vitro. PET imaging revealed high tumor specificity for both probes in vivo. In vivo and ex vivo NIR-II fluorescence imaging enabled accurate visualisation of tumor margins, with IRDye800CW-3BP-3940 exhibiting superior performance compared with IRDye800CW-FAP-2286. In the clinical specimen, IRDye800CW-3BP-3940 successfully delineated tumor regions with strong concordance to histopathological findings.</p><p><strong>Conclusion: </strong>We developed and validated a novel dual-modality molecular probe, IRDye800CW-3BP-3940, which integrated PET and NIR fluorescence imaging capabilities. This probe enabled highly specific detection of FAP-positive tumors and precise delineation of tumor margins in resected specimens.</p>\",\"PeriodicalId\":11909,\"journal\":{\"name\":\"European Journal of Nuclear Medicine and Molecular Imaging\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":7.6000,\"publicationDate\":\"2025-08-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Nuclear Medicine and Molecular Imaging\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00259-025-07512-8\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Nuclear Medicine and Molecular Imaging","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00259-025-07512-8","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Preclinical and pilot clinical evaluation of novel dual-modality pet/fluorescence probes targeting FAP for accurate tumor margin delineation.
Purpose: Accurate delineation of tumor margins and maximal safe resection are critical for successful curative oncologic surgery. However, fibroblast activation protein (FAP)-targeted probes suitable for fluorescence imaging remain limited. Here, we developed novel FAP-targeted fluorescent probes to accurately delineate tumor margins and enable rapid intraoperative identification of tumor boundaries in resected specimens.
Methods: DOTA chelator for radiolabelling with gallium-68 was incorporated into dual-modality FAP-targeted probes synthesised by conjugating FAP-2286 and 3BP-3940 with the near-infrared (NIR) fluorophore IRDye800CW. These probes were evaluated both in vitro and in vivo using HEK293T-FAP cells stably expressing FAP and xenograft mouse models. Positron emission tomography (PET) and (NIR-II) fluorescence imaging assessed the specificity and ability of probes to delineate tumor margins. For clinical validation, resected lung tissue was incubated ex vivo with the probes. Tumor regions and margins were identified using fluorescence imaging and subsequently validated by haematoxylin and eosin (H&E) staining and FAP immunohistochemistry.
Results: Both IRDye800CW-FAP-2286 and IRDye800CW-3BP-3940 exhibited high affinity for FAP-positive cells in vitro. PET imaging revealed high tumor specificity for both probes in vivo. In vivo and ex vivo NIR-II fluorescence imaging enabled accurate visualisation of tumor margins, with IRDye800CW-3BP-3940 exhibiting superior performance compared with IRDye800CW-FAP-2286. In the clinical specimen, IRDye800CW-3BP-3940 successfully delineated tumor regions with strong concordance to histopathological findings.
Conclusion: We developed and validated a novel dual-modality molecular probe, IRDye800CW-3BP-3940, which integrated PET and NIR fluorescence imaging capabilities. This probe enabled highly specific detection of FAP-positive tumors and precise delineation of tumor margins in resected specimens.
期刊介绍：
The European Journal of Nuclear Medicine and Molecular Imaging serves as a platform for the exchange of clinical and scientific information within nuclear medicine and related professions. It welcomes international submissions from professionals involved in the functional, metabolic, and molecular investigation of diseases. The journal's coverage spans physics, dosimetry, radiation biology, radiochemistry, and pharmacy, providing high-quality peer review by experts in the field. Known for highly cited and downloaded articles, it ensures global visibility for research work and is part of the EJNMMI journal family.
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