GDMPA Key Laboratory for Quality Control and Evaluation of Radiopharmaceuticals, PET Center and Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Eur J Nucl Med Mol Imaging. 2023 Sep;50(11):3363-3374. doi: 10.1007/s00259-023-06282-5. Epub 2023 Jun 2.
Research on fibroblast activating protein (FAP)-targeting inhibitor (FAPI) has become an important focus for cancer imaging and radiotherapy. Quinoline-based tracers [ Ga]FAPI-04 and [F]FAPI-42 have been widely used for positron emission tomography (PET) imaging of most tumors. However, there exist some limitations of these tracers with high uptake in biliary duct system and unstable uptake in pancreas, unsuitable for abdominal tumors PET imaging. Here we developed a [F]-labeled glycopeptide-containing FAPI tracer (named [F]FAPT) for PET imaging of FAP in cancers.
[F]FAPT was synthesized manually and automatically. The competitive binding to FAP, cellular internalization, and efflux characteristics were examined in vitro using A549-FAP cells. Dynamic MicroPET and biodistribution studies of [F]FAPT were then conducted in A549-FAP and U87MG xenograft tumor mouse models compared with [F]FAPI-42. Five healthy volunteers and three patients with cancer underwent [F]FAPT PET/CT.
Preclinical and clinical studies showed specific binding of [F]FAPT to FAP and favorable pharmacokinetic properties with better hydrophilicity, lower uptake in biliary duct system, higher tumor uptake and longer tumor retention compared with [F]FAPI-42. The biodistribution of [F]FAPT in healthy volunteers and patients with cancer displayed low uptake in most normal tissues except for pancreas, thyroid and salivary gland, which could contribute to high tumor-to-background ratios in most cancers.
[F]FAPT is better PET tracer than [F]FAPI-42 for imaging of biliary duct system cancer, potentially providing a tool to examine FAP expression in most cancers with high tumor-to-background ratios.
成纤维细胞激活蛋白（FAP）靶向抑制剂（FAPI）的研究已成为癌症成像和放射治疗的重要焦点。基于喹啉的示踪剂[68Ga]FAPI-04 和 [18F]FAPI-42 已广泛用于大多数肿瘤的正电子发射断层扫描（PET）成像。然而，这些示踪剂存在一些局限性，如在胆管系统中摄取较高，在胰腺中摄取不稳定，不适合腹部肿瘤的 PET 成像。在这里，我们开发了一种用于 FAP 在癌症中 PET 成像的[18F]标记的糖肽 FAPI 示踪剂（命名为[18F]FAPT）。
手动和自动合成 [18F]FAPT。使用 A549-FAP 细胞体外研究其与 FAP 的竞争结合、细胞内化和外排特性。然后在 A549-FAP 和 U87MG 异种移植肿瘤小鼠模型中与 [18F]FAPI-42 进行了[18F]FAPT 的动态 microPET 和生物分布研究。五位健康志愿者和三位癌症患者接受了 [18F]FAPT PET/CT 检查。
临床前和临床研究表明，[18F]FAPT 与 FAP 具有特异性结合，具有更好的亲水性、胆管系统摄取较低、肿瘤摄取较高和肿瘤保留时间较长等优点，与 [18F]FAPI-42 相比。健康志愿者和癌症患者的 [18F]FAPT 生物分布显示，除胰腺、甲状腺和唾液腺外，大多数正常组织的摄取较低，这有助于大多数癌症中获得较高的肿瘤与背景比值。
[18F]FAPT 是比 [18F]FAPI-42 更好的 PET 示踪剂，可用于胆管系统癌的成像，有可能提供一种工具来检查大多数癌症中 FAP 的表达，获得较高的肿瘤与背景比值。
