Banihashemian Seyedeh Somayyeh, Divband Ghasemali, Pirayesh Elahe, Nikkholgh Babak, Amini Hamidreza, Shahrnoy Abdolghafar Abolhosseini, Nami Reza, Akbari Mohammad Esmaeil
Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Khatam PET-CT Center, Khatam Hospital, Tehran, Iran.
Eur J Nucl Med Mol Imaging. 2024 Jun;51(7):1981-1988. doi: 10.1007/s00259-024-06635-8. Epub 2024 Feb 20.
Fibroblast activation protein (FAP) has emerged as a promising target for diagnosis and therapeutic intervention due to high expression and accumulation in the stromal compartments of a variety of malignant tumors. FAP-2286 utilizes cyclic peptides with FAP-binding characteristics to enhance the retention of the imaging agent within tumors, in contrast to the small-molecule FAP inhibitors (FAPI) like FAPI-04/46. The aim of this study was to quantify the tumor uptake of [Ga] Gallium-FAP-2286 within primary solid tumors, adjacent excised tissues, and metastatic lesions.
In this prospective study, 21 patients (average age 51.9) with various diagnoses of remaining and metastatic cancers participated. Among them, six had metastatic sarcoma, and 14 had adenocarcinoma, including eight breast, two rectum, two lung, two pancreas, and one thyroid cases. The patients underwent a [Ga]Ga-FAP-2286 PET/CT scan. An hour post-administration of [Ga]Ga-FAP-2286, a visual assessment of whole body scans and semi-quantification of the PET/CT results were carried out. The standardized uptake values (SUV) of [Ga]Ga-FAP-2286 in tumor lesions and the tumor-to-background ratio (TBR) were then calculated.
The vital signs of the patients, such as heart rate, blood pressure, and temperature, were observed before, during, and after the diagnostic procedure during the 4-h follow-up. All individuals underwent the [Ga]Ga-FAP-2286 PET/CT scans without any signs of drug-associated pharmacological effects. The PET/CT scans displayed substantial absorption of [Ga]Ga-FAP-2286 in tumor lesions in all patients (100% (21/21)). Irrespective of the tumors' origins (epithelial or mesothelium) and whether they exhibited local recurrence, distant recurrence, or metastatic lesions, the PET/CT scans revealed the uptake of [Ga]Ga-FAP-2286 in these lesions.
Overall, these data suggest that [Ga]Ga-FAP-2286 is a promising FAP derivative for efficient metastatic cancer diagnosis and being considered as a potential compound for therapeutic application in patients with advanced metastatic cancers.
成纤维细胞活化蛋白（FAP）由于在多种恶性肿瘤的基质区域高表达和聚集，已成为诊断和治疗干预的一个有前景的靶点。与小分子FAP抑制剂（如FAPI - 04/46）不同，FAP - 2286利用具有FAP结合特性的环肽来增强成像剂在肿瘤内的滞留。本研究的目的是量化[镓]镓 - FAP - 2286在原发性实体瘤、相邻切除组织和转移灶中的肿瘤摄取情况。
在这项前瞻性研究中，21例患有各种残留和转移性癌症诊断的患者（平均年龄51.9岁）参与其中。其中，6例患有转移性肉瘤，14例患有腺癌，包括8例乳腺癌、2例直肠癌、2例肺癌、2例胰腺癌和1例甲状腺癌病例。患者接受了[镓]镓 - FAP - 2286 PET/CT扫描。在给予[镓]镓 - FAP - 2286一小时后，对全身扫描进行视觉评估并对PET/CT结果进行半定量分析。然后计算肿瘤病变中[镓]镓 - FAP - 2286的标准化摄取值（SUV）和肿瘤与背景比值（TBR）。
在4小时随访期间，在诊断过程之前、期间和之后观察患者的生命体征，如心率、血压和体温。所有个体均接受了[镓]镓 - FAP - 2286 PET/CT扫描，未出现任何与药物相关的药理作用迹象。PET/CT扫描显示所有患者（100%（21/21））的肿瘤病变中[镓]镓 - FAP - 2286有大量摄取。无论肿瘤起源（上皮或间皮）以及它们是否表现出局部复发﹑远处复发或转移灶，PET/CT扫描均显示这些病变中摄取了[镓]镓 - FAP - 2286。
总体而言，这些数据表明[镓]镓 - FAP - 2286是一种有前景的FAP衍生物，可用于有效的转移性癌症诊断，并被认为是晚期转移性癌症患者治疗应用的潜在化合物。
