Medullary thyroid carcinoma (MTC) can only be cured through the excision of all metastatic lesions, but 29-60% patients failed to localize the disease in the current clinical practice. 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]FDG PET-CT in 50 MTC patients. 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 (SUVmax 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 to [18F]FDG (96.7% vs. 43.3%, p<0.0001). Notably, 32% patients altered management following [68Ga]Ga-CTR-FAPI PET-CT, and 66.7% patients changed their surgical plan. Overall, [68Ga]Ga-CTR-FAPI PET-CT provided superior detection and diagnostic accuracy compared to [18F]FDG PET-CT, enabling precision management of MTC patients.

中文翻译：

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CTR-FAPI PET 实现甲状腺髓样癌的精准管理


甲状腺髓样癌 （MTC） 只能通过切除所有转移病灶来治愈，但在目前的临床实践中，29-60% 的患者未能定位疾病。以前，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），以提高检测灵敏度和准确性。在这项一流的临床试验中，我们在 50 名 MTC 患者中对 [68Ga]Ga-CTR-FAPI PET-CT 和 [18F]FDG PET-CT 进行了头对头比较。主要终点是基于患者的检出率，[68Ga]Ga-CTR-FAPI 的检出率高于 [18F]FDG（98% 对 66%，p=0.0002）。这种改进的检测归因于肿瘤摄取增加 （SUVmax 11.71±9.16 vs. 2.55±1.73，p<0.0001）。与 [18F]FDG 相比，[68Ga]Ga-CTR-FAPI 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 [68Ga]Ga-CTR-FAPI PET-CT 后改变了治疗，66.7% 的患者改变了手术计划。总体而言，与 [18F]FDG PET-CT 相比，[68Ga]Ga-CTR-FAPI PET-CT 提供了卓越的检测和诊断准确性，能够对 MTC 患者进行精确管理。