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优化 177 镥-抗碳酸酐酶 IX 放射性免疫疗法在腹腔透明细胞肾细胞癌异种移植模型中的应用。

Optimizing lutetium 177-anti-carbonic anhydrase IX radioimmunotherapy in an intraperitoneal clear cell renal cell carcinoma xenograft model.

出版信息

Mol Imaging. 2014;13:1-7.

PMID:24824962
Abstract

A new approach in the treatment of clear cell renal carcinoma (ccRCC) is radioimmunotherapy (RIT) using anti-carbonic anhydrase IX (CAIX) antibody G250. To investigate the potential of RIT with lutetium 177 (177Lu)-labeled G250, we conducted a protein dose escalation study and subsequently an RIT study in mice with intraperitoneally growing ccRCC lesions. Mice with intraperitoneal xenografts were injected with 1, 3, 10, 30, or 100 μg of G250 labeled with 10 MBq indium 111 (111In) to determine the optimal protein dose. The optimal protein dose determined with imaging and biodistribution studies was used in a subsequent RIT experiment in three groups of 10 mice with intraperitoneal SK-RC-52 tumors. One group received 13 MBq 177Lu-DOTA-G250, a control group received 13 MBq nonspecific 177Lu-MOPC21, and the second control group was not treated and received 20 MBq 111In-DOTA-G250. The optimal G250 protein dose to target ccRCC in this model was 10 μg G250. Treatment with 13 MBq 177Lu-DOTA-G250 was well tolerated and resulted in significantly prolonged median survival (139 days) compared to controls (49-53 days, p  =  .015), indicating that RIT has potential in this metastatic ccRCC model.

摘要

一种治疗肾透明细胞癌 (ccRCC) 的新方法是使用抗碳酸酐酶 IX (CAIX) 抗体 G250 的放射免疫疗法 (RIT)。为了研究用镥 177(177Lu)标记的 G250 的 RIT 潜力,我们进行了一项蛋白剂量递增研究,随后在腹腔内生长 ccRCC 病变的小鼠中进行了 RIT 研究。将腹腔异种移植物的小鼠注射 1、3、10、30 或 100 μg 用 10 MBq 铟 111(111In)标记的 G250,以确定最佳蛋白剂量。通过成像和生物分布研究确定的最佳蛋白剂量用于随后的腹腔 SK-RC-52 肿瘤的三组 10 只小鼠的 RIT 实验。一组接受 13 MBq 177Lu-DOTA-G250,对照组接受 13 MBq 非特异性 177Lu-MOPC21,第二个对照组未治疗并接受 20 MBq 111In-DOTA-G250。该模型中靶向 ccRCC 的最佳 G250 蛋白剂量为 10 μg G250。与对照组(49-53 天,p =.015)相比,接受 13 MBq 177Lu-DOTA-G250 治疗的小鼠耐受性良好,中位生存期显著延长(139 天),表明 RIT 在此转移性 ccRCC 模型中具有潜力。

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