Purpose

To identify the biodistribution and diagnostic performance of a novel fibroblast activation protein (FAP) targeted positron emission tomography (PET) tracer, [⁶⁸Ga]Ga-DOTA-GPFAPI-04, in patients with solid tumors in a head-to-head comparison with [¹⁸F]F-FDG.

Methods

Twenty-six patients histologically proven with cancers of nasopharyngeal (n = 5), esophagus (n = 5), gastro-esophagus (n = 1), stomach (n = 7), liver (n = 3), and colorectum (n = 5) were recruited for [⁶⁸Ga]Ga-DOTA-GPFAPI-04 and [¹⁸F]F-FDG PET/CT scans on consecutive days. The primary endpoint was the diagnostic efficacy, with the histological diagnosis and the follow-up results selected as the gold standard. The secondary endpoint was the background uptake pattern. Two experienced nuclear medicine physicians who were blinded to the gold standard results while having essential awareness of the clinical context reviewed the images and labeled lesions by consensus for subsequent software-assisted lesion segmentation. Additionally, background organs were automatically segmented, assisted by artificial intelligence. Volume, mean, and maximum standard uptake values (SUVmean and SUVmax) of all segmentations were recorded. P < 0.05 was deemed as statistically significant.

Results

Significant glandular uptake of [⁶⁸Ga]Ga-DOTA-GPFAPI-04 was detected in the thyroid, pancreas, and submandibular glands, while moderate uptake was observed in the parotid glands. The myocardium and myometrium exhibited 2–3 times higher uptake of the radiotracer than that of the background levels in blood and liver. A total of 349 targeted lesions, consisting of 324 malignancies and 25 benign lesions, were segmented. [⁶⁸Ga]Ga-DOTA-GPFAPI-04 is more sensitive than [¹⁸F]F-FDG, especially for abdominopelvic dissemination (1.000 vs. 0.475, P < 0.001). Interestingly, [¹⁸F]F-FDG demonstrated higher sensitivity for lung metastasis compared to [⁶⁸Ga]Ga-DOTA-GPFAPI-04 (0.845 vs. 0.682, P = 0.003). The high glandular uptake made it difficult to delineate lesions in close proximity and masked two metastatic lesions in these organs.

Conclusion

Despite prominent glandular uptake, [⁶⁸Ga]Ga-DOTA-GPFAPI-04 demonstrates favorable diagnostic performance. It is a promising probe scaffold for further development of FAP-targeted tumor theranostic agents.

中文翻译：

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[68Ga]Ga-DOTA-GPFAPI-04 与 [18F]F-FDG 对实体瘤患者的诊断功效进行头对头比较：前瞻性临床研究结果

目的

通过头对头比较来确定新型成纤维细胞激活蛋白 (FAP) 靶向正电子发射断层扫描 (PET) 示踪剂 [ ⁶⁸ Ga]Ga-DOTA-GPFAPI-04 在实体瘤患者中的生物分布和诊断性能与[ ¹⁸ F]F-FDG。

方法

26 名患者经组织学证实患有鼻咽癌 ( n  = 5)、食道癌 ( n  = 5)、胃食道癌 ( n  = 1)、胃癌 ( n  = 7)、肝癌 ( n  = 3) 和结直肠癌 ( n = 3)  = 5) 被招募连续几天进行 [ ⁶⁸ Ga]Ga-DOTA-GPFAPI-04 和 [ ¹⁸ F]F-FDG PET/CT 扫描。主要终点为诊断效能，选择组织学诊断和随访结果作为金标准。次要终点是背景摄取模式。两名经验丰富的核医学医生对金标准结果不知情，但对临床背景有基本的认识，他们审查了图像并一致标记了病灶，以便随后进行软件辅助病灶分割。此外，在人工智能的辅助下，背景器官被自动分割。记录所有分段的体积、平均值和最大标准摄取值（SUVmean 和 SUVmax）。P  <0.05被认为具有统计学意义。

结果

^{在甲状腺、胰腺和颌下腺中检测到[ 68} Ga]Ga-DOTA-GPFAPI-04的显着腺体摄取，而在腮腺中观察到中等摄取。心肌和子宫肌层对放射性示踪剂的吸收量比血液和肝脏中的背景水平高 2-3 倍。总共分割了 349 个目标病灶，其中包括 324 个恶性肿瘤和 25 个良性病灶。 [ ^{68 Ga]Ga-DOTA-GPFAPI-04 比 [ 18} F]F-FDG更敏感，特别是对于腹盆腔播散（1.000 vs. 0.475，P  < 0.001）。有趣的是，与[ ⁶⁸ Ga]Ga-DOTA-GPFAPI-04相比， [ ^{18 F]F-FDG 对肺转移表现出更高的敏感性（0.845 vs. 0.682，} P  = 0.003）。腺体的高摄取使得很难描绘出邻近的病灶，并掩盖了这些器官中的两个转移病灶。

结论

尽管腺体摄取显着，[ ⁶⁸ Ga]Ga-DOTA-GPFAPI-04 显示出良好的诊断性能。它是一种很有前途的探针支架，可用于进一步开发 FAP 靶向肿瘤治疗试剂。