Deutsch-Williams Riley J, Schleyer Kelton A, Das Riddha, Carrothers Jasmine E, Kohler Rainer H, Vinegoni Claudio, Weissleder Ralph
Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, Massachusetts 02114, United States.
Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, United States.
Bioconjug Chem. 2025 Jan 15;36(1):44-53. doi: 10.1021/acs.bioconjchem.4c00426. Epub 2024 Dec 12.
Cancer-associated fibroblasts (CAFs) expressing fibroblast activation protein alpha (FAP) are abundant in tumor microenvironments and represent an emerging target for PET cancer imaging. While different quinolone-based small molecule agents have been developed for whole-body imaging, there is a scarcity of well-validated fluorescent small molecule imaging agents to better study these cells in vivo. Here, we report the synthesis and characterization of a series of fluorescent FAP imaging agents based on the common quinolone azide inhibitor. Our data show excellent performance of some synthesized FAP Targeting Fluorescent probes (FTFs) for both topical application and intravenous delivery to label CAF populations in solid tumors. These results suggest that FTF can be used to study CAF biology and therapeutic targeting in vivo.
表达成纤维细胞活化蛋白α（FAP）的癌症相关成纤维细胞（CAF）在肿瘤微环境中大量存在，是正电子发射断层扫描（PET）癌症成像的一个新兴靶点。虽然已经开发了不同的基于喹诺酮的小分子试剂用于全身成像，但缺乏经过充分验证的荧光小分子成像试剂来更好地在体内研究这些细胞。在此，我们报告了一系列基于常见喹诺酮叠氮化物抑制剂的荧光FAP成像试剂的合成与表征。我们的数据显示，一些合成的FAP靶向荧光探针（FTF）在局部应用和静脉注射以标记实体瘤中的CAF群体方面均表现出优异的性能。这些结果表明，FTF可用于在体内研究CAF生物学和治疗靶点。
