Purpose

Fibroblast-activated protein (FAP) is highly expressed in cancer-associated fibroblasts (CAFs) of many solid cancers, but low or absent in normal tissues. Our study aimed to develop a novel FAP-specific tracer, namely [¹⁸F]FAP-2286, and evaluated its performance in comparison with well-established agents such as [¹⁸F]FAPI-42 and [⁶⁸Ga]Ga-FAP-2286 in preclinical research, as well as 2-[¹⁸F]FDG in pilot clinical study.

Methods

[¹⁸F]FAP-2286 was manually synthesized in accordance with Good Manufacturing Practice (GMP). Subsequent investigations encompassed cell uptake, competitive binding affinity, internalization and efflux assays using HT-1080hFAP cell lines. PET imaging and biodistribution studies were conducted in HEK-293ThFAP, A549hFAP, HT-1080hFAP tumor-bearing mice as well as HEK-293T, A549 and HT-1080 control groups. Furthermore, clinical evaluation of [¹⁸F]FAP-2286 was performed in fifteen patients with various cancers compared to 2-[¹⁸F]FDG PET.

Results

The radiolabeling yield of [¹⁸F]FAP-2286 was 30.53 ± 5.20%, with a radiochemical purity exceeding 97%. In cell assays, [¹⁸F]FAP-2286 showed specific uptake, high internalization fraction and low cellular efflux. Rapid tumor uptake and satisfactory tumor retention was observed on micro-PET imaging and cancer patients. Meanwhile, the clinical research demonstrated that [¹⁸F]FAP-2286 may represent an alternative for low glucose-metabolism malignant tumors PET imaging such as gastric cancers.

Conclusion

[¹⁸F]FAP-2286 showed superior imaging quality including rapid and high target uptake and satisfactory retention in both tumor-bearing mice and cancer patients. It may emerge as a promising candidate for early or delayed phase imaging and 2-[¹⁸F]FDG non-avid cancers PET scan.

中文翻译：

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[18F]FAP-2286的临床前研究和首次人体成像，以及与2-[18F]FDG PET/CT在各种癌症患者中的比较

目的

成纤维细胞激活蛋白（FAP）在许多实体癌的癌症相关成纤维细胞（CAF）中高表达，但在正常组织中低表达或不表达。我们的研究旨在开发一种新型 FAP 特异性示踪剂，即 [ ¹⁸ F]FAP-2286，并与 [ ¹⁸ F]FAPI-42 和 [ ⁶⁸ Ga]Ga-FAP-等成熟药物相比评估其性能。第2286章 临床前研究，以及2-[ ¹⁸ F]FDG的试点临床研究。

方法

[ ¹⁸ F]FAP-2286是根据良好生产规范（GMP）手动合成的。随后的研究包括使用 HT-1080hFAP 细胞系进行细胞摄取、竞争性结合亲和力、内化和外排测定。在 HEK-293ThFAP、A549hFAP、HT-1080hFAP 荷瘤小鼠以及 HEK-293T、A549 和 HT-1080 对照组中进行 PET 成像和生物分布研究。此外，与 2-[ ^{18 F]FDG PET 相比，对 15 名患有各种癌症的患者进行了 [ 18} F]FAP-2286 的临床评估。

结果

^{[ 18} F]FAP-2286的放射性标记产率为30.53±5.20%，放射化学纯度超过97%。在细胞测定中，[ ¹⁸ F]FAP-2286 显示出特异性摄取、高内化分数和低细胞流出。在微型 PET 成像和癌症患者中观察到快速的肿瘤摄取和令人满意的肿瘤保留。同时，临床研究表明，[ ¹⁸ F]FAP-2286可能成为胃癌等低糖代谢恶性肿瘤PET成像的替代方案。

结论

[ ¹⁸ F]FAP-2286 在荷瘤小鼠和癌症患者中显示出卓越的成像质量，包括快速且高的靶标摄取和令人满意的保留。它可能成为早期或延迟阶段成像和 2-[ ¹⁸ F]FDG 非活跃癌症 PET 扫描的有前途的候选者。