Department of Nuclear Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India (S.C., Y.M., N.R., H.S., R.K., J.S., B.R.M.).
Department of Chemistry, Johannes Gutenberg University, Mainz, Germany (F.R., E.S.M.).
Acad Radiol. 2024 Jun;31(6):2521-2535. doi: 10.1016/j.acra.2023.12.002. Epub 2024 Jan 16.
Fibroblast Activation Protein (FAP) expressing cancer-associated fibroblasts has been a major breakthrough causing a paradigm shift in targeted theranostics focusing on the tumor microenvironment. In this study, a squaric acid derivative DOTA.SA.FAPi (SA.FAPi) has been evaluated as a potential diagnostic probe in diverse epithelial cancers and compared to the standard-of-care F-FDG.
25 patients enrolled in this prospective study underwent F-FDG and Ga-SA.FAPi PET scans on two different days. For biodistribution, standardized uptake values (SUV) were computed by delineating region-of-interest on various body organs. For comparative analysis in disease identification, lesion tracer uptake was quantified using SUVs corrected for lean body mass (SUL), SUV, tumor-to-background ratio (TBR) with liver and blood pool as the reference, total lesion glycolysis (TLG for F-FDG) and total lesion FAP expression (TLF for Ga-SA.FAPi).
25 patients (mean age: 58 ± 8 years) with four types of cancers including hepatocellular carcinoma (HCC, 56% of cohort), gall bladder carcinoma (GB Ca, 12%), adrenocortical carcinoma (ACC, 16%), and breast carcinoma (breast Ca, 16%) were prospectively evaluated. Physiological tracer uptake of Ga-SA.FAPi was noted in the salivary glands, thyroid, liver, pancreas, muscles and kidneys with variable uptake in the lacrimal glands, extra-ocular muscles, oral mucosa and uterus. Lesion-based comparative analysis between both the radiotracers demonstrated complete concordant findings in detection of all primary lesions and distant metastases in liver, bones, adrenals and peritoneum whereas discordant findings were noted in lung nodules (20%) and lymph nodes (13%). In overall analysis, Ga-SA.FAPi exhibited significantly higher SUV (10.3 vs 8.8, p-0.019), SUL (6.8 vs 4.9, p-0.000) and SUL (5.4 vs 4.1, p-0.019) in comparison to F-FDG whereas TBR was comparable for both the tracers [TBR: median 1.9 (IQR: 2.6-1.4) vs 1.8 (2.6-1.1), p-0.275; TBR: 2.1 (3.7-1.4) vs 2.0 (2.7-1.4), p-0.207]. In subcategorical analysis, Ga-SA.FAPi demonstrated higher SUV, SUL and SUL values for primary disease (SUV: 14.8 (18.7-9.7) vs (12.9-6.6), p-0.087; SUL: 8.2 (11.2-6.8) vs 6.3 (8.5-4.4), p-0.037; SUL: 6.9 ± 2.5 vs 5.1 ± 2.2, p-0.023] and distant metastases (8.8 vs 7.2, p-0.038); 6.3 (8.8-4.4) vs 3.6 (4.4-2.0), p-0.000; 5.4 vs 3.5, p-0.000] whereas comparable values were noted for both the tracers in nodal metastases [9 (13.5-4.1) vs 8 (12.7-4.7), p-0.726; 4.5 (6.2-1.8) vs 4.3 (5.7-2.2), p-0.727; 4.1 ± 2.3 vs 3.7 ± 1.8, p-0.129]. In primary disease, highest Ga-SA.FAPi avidity was noted in ACC followed by GB Ca and HCC. In distant metastases, gall bladder, lung and skeletal lesions demonstrated higher Ga-SA.FAPi avidity. Moreover, Ga-SA.FAPi identified five additional lung lesions which were missed by F-FDG in one case of ACC.
Ga-SA.FAPi emerged as an effective, versatile diagnostic probe for imaging various epithelial malignancies similar to F-FDG.
成纤维细胞激活蛋白（FAP）在表达癌症相关成纤维细胞的研究中取得了重大突破，促使针对肿瘤微环境的靶向治疗发生了范式转变。在这项研究中，一种新型的方酸衍生物 DOTA.SA.FAPi（SA.FAPi）已被评估为一种有潜力的诊断探针，可用于多种上皮癌，并与标准的 F-FDG 进行比较。
25 名患者参与了这项前瞻性研究，在两天内接受了 F-FDG 和 Ga-SA.FAPi PET 扫描。为了进行生物分布分析，通过勾画各器官的感兴趣区域，计算标准化摄取值（SUV）。为了进行疾病识别的对比分析，使用 SUV 校正后的瘦体重（SUL）、SUV、肿瘤与背景比（TBR），以肝和血池为参照，总病灶糖酵解（TLG 用于 F-FDG）和总病灶 FAP 表达（TLF 用于 Ga-SA.FAPi）来量化病变示踪剂摄取。
25 名患者（平均年龄：58±8 岁），包括 4 种类型的癌症，包括肝细胞癌（HCC，占队列的 56%）、胆囊癌（GB Ca，占 12%）、肾上腺皮质癌（ACC，占 16%）和乳腺癌（breast Ca，占 16%），前瞻性地进行了评估。Ga-SA.FAPi 在唾液腺、甲状腺、肝脏、胰腺、肌肉和肾脏中显示出生理性示踪剂摄取，在泪腺、眼外肌、口腔黏膜和子宫中摄取量不同。两种放射性示踪剂的基于病变的对比分析显示，在检测肝、骨、肾上腺和腹膜的所有原发性病变和远处转移方面，两种示踪剂的结果完全一致，而在肺结节（20%）和淋巴结（13%）方面的结果不一致。总的来说，与 F-FDG 相比，Ga-SA.FAPi 显示出更高的 SUV（10.3 比 8.8，p-0.019）、SUL（6.8 比 4.9，p-0.000）和 SUL（5.4 比 4.1，p-0.019），而 TBR 两种示踪剂之间无差异[TBR：中位数 1.9（IQR：2.6-1.4）比 1.8（2.6-1.1），p-0.275；TBR：2.1（3.7-1.4）比 2.0（2.7-1.4），p-0.207]。在亚分类分析中，Ga-SA.FAPi 在原发性疾病（SUV：14.8（18.7-9.7）比（12.9-6.6），p-0.087；SUL：8.2（11.2-6.8）比 6.3（8.5-4.4），p-0.037；SUL：6.9±2.5 比 5.1±2.2，p-0.023）和远处转移（SUV：8.8 比 7.2，p-0.038；SUL：6.3（8.8-4.4）比 3.6（4.4-2.0），p-0.000；SUL：5.4 比 3.5，p-0.000）中显示出更高的 SUV、SUL 和 SUL 值，而在淋巴结转移中，两种示踪剂的结果相似[9（13.5-4.1）比 8（12.7-4.7），p-0.726；4.5（6.2-1.8）比 4.3（5.7-2.2），p-0.727；4.1±2.3 比 3.7±1.8，p-0.129]。在原发性疾病中，ACC 中的 Ga-SA.FAPi 摄取最高，其次是胆囊癌和肝细胞癌。在远处转移中，胆囊、肺和骨骼病变显示出更高的 Ga-SA.FAPi 摄取。此外，Ga-SA.FAPi 在一名 ACC 患者中还发现了 5 个额外的 F-FDG 漏诊的肺部病变。
Ga-SA.FAPi 作为一种有效的、多功能的诊断探针，可用于成像多种上皮恶性肿瘤，与 F-FDG 相似。
