Treatment of patients with advanced medullary thyroid carcinoma (MTC) is still a challenge. For more than 2 decades, it has been known that the cholecystokinin 2 receptor is a promising target for the treatment of MTC with radiolabeled minigastrin analogs. Unfortunately, kidney toxicity has precluded their therapeutic application so far. In 6 consecutive patients, we evaluated with advanced 3-dimensional dosimetry whether improved minigastrin analog ¹⁷⁷Lu-DOTA-(d-Glu)₆-Ala-Tyr-Gly-Trp-Nle-Asp-PheNH₂ (¹⁷⁷Lu-PP-F11N) is a suitable agent for the treatment of MTC. Methods: Patients received 2 injections of about 1 GBq (∼80 μg) of ¹⁷⁷Lu-PP-F11N with and without a solution of succinylated gelatin (SG, a plasma expander used for nephroprotection) in a random crossover sequence to evaluate biodistribution, pharmacokinetics, and tumor and organ dosimetry. An electrocardiogram was obtained and blood count and blood chemistry were measured up to 12 wk after the administration of ¹⁷⁷Lu-PP-F11N to assess safety. Results: In all patients, ¹⁷⁷Lu-PP-F11N accumulation was visible in tumor tissue, stomach, and kidneys. Altogether, 13 tumors were eligible for dosimetry. The median absorbed doses for tumors, stomach, kidneys, and bone marrow were 0.88 (interquartile range [IQR]: 0.85–1.04), 0.42 (IQR: 0.25–1.01), 0.11 (IQR: 0.07–0.13), and 0.028 (IQR: 0.026–0.034) Gy/GBq, respectively. These doses resulted in median tumor-to-kidney dose ratios of 11.6 (IQR: 8.11–14.4) without SG and 13.0 (IQR: 10.2–18.6) with SG; these values were not significantly different (P = 1.0). The median tumor-to-stomach dose ratio was 3.34 (IQR: 1.14–4.70). Adverse reactions (mainly hypotension, flushing, and hypokalemia) were self-limiting and not higher than grade 1. Conclusion: ¹⁷⁷Lu-PP-F11N accumulates specifically in MTC at a dose that is sufficient for a therapeutic approach. With a low kidney and bone marrow radiation dose, ¹⁷⁷Lu-PP-F11N shows a promising biodistribution. The dose-limiting organ is most likely the stomach. Further clinical studies are necessary to evaluate the maximum tolerated dose and the efficacy of ¹⁷⁷Lu-PP-F11N.

晚期甲状腺髓样癌（MTC）患者的治疗仍然是一个挑战。二十多年来，人们已经知道胆囊收缩素2受体是用放射性标记的小胃泌素类似物治疗MTC的有希望的靶标。不幸的是，到目前为止，肾脏毒性阻止了它们的治疗应用。在连续的6例患者中，我们用先进的3维剂量测定法评估了minigastrin类似物¹⁷⁷ Lu-DOTA-（d - Glu）₆ -Ala-Tyr-Gly-Trp-Nle-Asp-PheNH ₂（¹⁷⁷ Lu-PP-F11N ）是治疗MTC的合适药物。方法：患者接受2次注射，每次注射约1 GBq（〜80μg）¹⁷⁷Lu-PP-F11N，有和没有琥珀酰明胶（SG，一种用于肾保护的血浆扩展剂）溶液，以随机交叉顺序进行，以评估生物分布，药代动力学以及肿瘤和器官剂量。在服用¹⁷⁷ Lu-PP-F11N后至12周为止，均获得了心电图，并测量了血液计数和血液化学，以评估安全性。结果：在所有患者中，¹⁷⁷Lu-PP-F11N的积累在肿瘤组织，胃和肾脏中可见。总共有13个肿瘤符合剂量学标准。肿瘤，胃，肾和骨髓的平均吸收剂量为0.88（四分位间距[IQR]：0.85–1.04），0.42（IQR：0.25–1.01），0.11（IQR：0.07–0.13）和0.028（IQR） ：0.026–0.034）Gy / GBq。这些剂量导致没有SG的肿瘤与肾脏的中位剂量比为11.6（IQR：8.11-14.4），而有SG的中位数为13.0（IQR：10.2-18.6）；这些值没有显着差异（P = 1.0）。肿瘤与胃的中位剂量比为3.34（IQR：1.14–4.70）。不良反应（主要是低血压，潮红和低钾血症）是自限性的，不高于1级。结论： ¹⁷⁷Lu-PP-F11N专门以足以用于治疗的剂量在MTC中积累。¹⁷⁷ Lu-PP-F11N具有较低的肾脏和骨髓辐射剂量，显示出良好的生物分布。剂量限制器官很可能是胃。需要进一步的临床研究以评估¹⁷⁷ Lu-PP-F11N的最大耐受剂量和疗效。