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Abstract：
Preclinical and clinical studies have indicated that somatostatin receptor (sst)-expressing tumors demonstrate higher uptake of radiolabeled sst antagonists than of sst agonists. In 4 consecutive patients with advanced neuroendocrine tumors, we evaluated whether treatment with (177)Lu-labeled sst antagonists is feasible.
METHODS: After injection of approximately 1 GBq of (177)Lu-DOTA-[Cpa-c(DCys-Aph(Hor)-DAph(Cbm)-Lys-Thr-Cys)-DTyr-NH2] ((177)Lu-DOTA-JR11) and (177)Lu-DOTATATE, 3-dimensional voxel dosimetry analysis based on SPECT/CT was performed. A higher tumor-to-organ dose ratio for (177)Lu-DOTA-JR11 than for (177)Lu-DOTATATE was the prerequisite for treatment with (177)Lu-DOTA-JR11.
RESULTS: Reversible minor adverse effects of (177)Lu-DOTA-JR11 were observed. (177)Lu-DOTA-JR11 showed a 1.7-10.6 times higher tumor dose than (177)Lu-DOTATATE. At the same time, the tumor-to-kidney and tumor-to-bone marrow dose ratio was 1.1-7.2 times higher. All 4 patients were treated with (177)Lu-DOTA-JR11, resulting in partial remission in 2 patients, stable disease in 1 patient, and mixed response in the other patient.
CONCLUSIONS: Treatment of neuroendocrine tumors with radiolabeled sst antagonists is clinically feasible and may have a significant impact on peptide receptor radionuclide therapy.
METHODS: After injection of approximately 1 GBq of (177)Lu-DOTA-[Cpa-c(DCys-Aph(Hor)-DAph(Cbm)-Lys-Thr-Cys)-DTyr-NH2] ((177)Lu-DOTA-JR11) and (177)Lu-DOTATATE, 3-dimensional voxel dosimetry analysis based on SPECT/CT was performed. A higher tumor-to-organ dose ratio for (177)Lu-DOTA-JR11 than for (177)Lu-DOTATATE was the prerequisite for treatment with (177)Lu-DOTA-JR11.
RESULTS: Reversible minor adverse effects of (177)Lu-DOTA-JR11 were observed. (177)Lu-DOTA-JR11 showed a 1.7-10.6 times higher tumor dose than (177)Lu-DOTATATE. At the same time, the tumor-to-kidney and tumor-to-bone marrow dose ratio was 1.1-7.2 times higher. All 4 patients were treated with (177)Lu-DOTA-JR11, resulting in partial remission in 2 patients, stable disease in 1 patient, and mixed response in the other patient.
CONCLUSIONS: Treatment of neuroendocrine tumors with radiolabeled sst antagonists is clinically feasible and may have a significant impact on peptide receptor radionuclide therapy.
摘要：
临床前和临床研究表明，表达生长抑素受体（sst）的肿瘤显示放射性标记的sst拮抗剂的摄取高于sst激动剂。在连续4例晚期神经内分泌肿瘤患者中，我们评估了用(177)Lu标记的sst拮抗剂治疗是否可行.
方法：注入约1GBq的（177）Lu-DOTA-[Cpa-c（DCys-Aph（Hor）-DAph（Cbm）-Lys-Thr-Cys）-DTyr-NH2]（（（177）Lu-DOTA-JR11）和（177）Lu-DOTATATE，基于SPECT/CT进行三维体素剂量测定分析。（177）Lu-DOTA-JR11比（177）Lu-DOTATATE更高的肿瘤器官剂量比是（177）Lu-DOTA-JR11治疗的先决条件。
结果：观察到（177）Lu-DOTA-JR11的可逆轻微不良反应。（177）Lu-DOTA-JR11的肿瘤剂量比（177）Lu-DOTATATE高1.7-10.6倍。同时,肿瘤与肾脏和肿瘤与骨髓的剂量比高1.1-7.2倍.所有4例患者均接受（177）Lu-DOTA-JR11治疗，导致2例患者部分缓解，1例患者病情稳定,和另一个病人的混合反应。
结论：使用放射性标记的sst拮抗剂治疗神经内分泌肿瘤在临床上是可行的，并且可能对肽受体放射性核素治疗产生重大影响。
方法：注入约1GBq的（177）Lu-DOTA-[Cpa-c（DCys-Aph（Hor）-DAph（Cbm）-Lys-Thr-Cys）-DTyr-NH2]（（（177）Lu-DOTA-JR11）和（177）Lu-DOTATATE，基于SPECT/CT进行三维体素剂量测定分析。（177）Lu-DOTA-JR11比（177）Lu-DOTATATE更高的肿瘤器官剂量比是（177）Lu-DOTA-JR11治疗的先决条件。
结果：观察到（177）Lu-DOTA-JR11的可逆轻微不良反应。（177）Lu-DOTA-JR11的肿瘤剂量比（177）Lu-DOTATATE高1.7-10.6倍。同时,肿瘤与肾脏和肿瘤与骨髓的剂量比高1.1-7.2倍.所有4例患者均接受（177）Lu-DOTA-JR11治疗，导致2例患者部分缓解，1例患者病情稳定,和另一个病人的混合反应。
结论：使用放射性标记的sst拮抗剂治疗神经内分泌肿瘤在临床上是可行的，并且可能对肽受体放射性核素治疗产生重大影响。
