Kong Ziren, Li Zhu, Cui Xi-Yang, Wang Jian, Xu Mengxin, Liu Yang, Chen Junyi, Ni Song, Zhang Zongmin, Fan Xiaowei, Huang Jiazhao, Lin Yansong, Sun Yuning, He Yuqin, Lin Xinfeng, Meng Tianyu, Li Han, Song Yixuan, Peng Boshizhang, An Changming, Gao Chenyan, Li Nan, Liu Chen, Zhu Yiming, Yang Zhi, Liu Zhibo, Liu Shaoyan
Department of Head and Neck Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Key Laboratory of Carcinogenesis and Translational Research, Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, China.
Cancer Discov. 2025 Feb 7;15(2):316-328. doi: 10.1158/2159-8290.CD-24-0897.
Medullary thyroid carcinoma (MTC) can only be cured through the excision of all metastatic lesions, but current clinical practice fails to localize the disease in 29% to 60% of patients. Previously, we developed a fibroblast activation protein inhibitor (FAPI)-based covalent targeted radioligand (CTR) for improved detection sensitivity and accuracy. In this first-in-class clinical trial, we head-to-head compared [68Ga]Ga-CTR-FAPI PET-CT and [18F]fluorodeoxyglucose ([18F]FDG) PET-CT in 50 patients with MTC. The primary endpoint was the patient-based detection rate, with [68Ga]Ga-CTR-FAPI exhibiting higher detection than [18F]FDG (98% vs. 66%, P = 0.0002). This improved detection was attributed to increased tumor uptake (maximum standardized uptake value = 11.71 ± 9.16 vs. 2.55 ± 1.73, P < 0.0001). Diagnostic accuracy, validated on lesions with gold-standard pathology, was greater for [68Ga]Ga-CTR-FAPI compared with [18F]FDG (96.7% vs. 43.3%, P < 0.0001). Notably, the management of 32% of patients was altered following [68Ga]Ga-CTR-FAPI PET-CT, and the surgical plan was changed for 66.7% of patients. Overall, [68Ga]Ga-CTR-FAPI PET-CT provided superior detection and diagnostic accuracy compared with [18F]FDG PET-CT, enabling precision management of patients with MTC. Significance: In this first-in-class clinical trial of CTR, [68Ga]Ga-CTR-FAPI demonstrated an improved patient-based detection rate (98%), tumor uptake (maximum standardized uptake value = 11.71 ± 9.16), and pathology-validated diagnostic accuracy (96.7%) compared with the currently approved method in MTC treatment. It directly altered management in 32% of patients, enabling precision diagnosis and management of MTC. See related commentary by Witney, p. 264.
甲状腺髓样癌（MTC）只能通过切除所有转移病灶来治愈，但目前的临床实践在29%至60%的患者中无法定位该疾病。此前，我们开发了一种基于成纤维细胞活化蛋白抑制剂（FAPI）的共价靶向放射性配体（CTR），以提高检测的灵敏度和准确性。在这项同类首个临床试验中，我们对50例MTC患者的[68Ga]Ga-CTR-FAPI PET-CT和[18F]氟脱氧葡萄糖（[18F]FDG）PET-CT进行了直接比较。主要终点是基于患者的检测率，[68Ga]Ga-CTR-FAPI的检测率高于[18F]FDG（98%对66%，P = 0.0002）。这种检测的改善归因于肿瘤摄取增加（最大标准化摄取值 = 11.71±9.16对2.55±1.73，P < 0.0001）。与[18F]FDG相比，[68Ga]Ga-CTR-FAPI在经金标准病理验证的病变上的诊断准确性更高（96.7%对43.3%，P < 0.0001）。值得注意的是，32%的患者在接受[68Ga]Ga-CTR-FAPI PET-CT检查后治疗方案发生了改变，66.7%的患者手术计划发生了变化。总体而言，与[18F]FDG PET-CT相比，[68Ga]Ga-CTR-FAPI PET-CT提供了更高的检测和诊断准确性，能够对MTC患者进行精准管理。意义：在这项CTR同类首个临床试验中，与MTC治疗中目前批准的方法相比，[68Ga]Ga-CTR-FAPI显示出基于患者的检测率提高（98%）、肿瘤摄取增加（最大标准化摄取值 = 11.71±9.16）以及经病理验证的诊断准确性提高（96.7%）。它直接改变了32%患者的治疗方案，实现了MTC的精准诊断和管理。见Witney的相关评论，第264页。
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