PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177Lu-Labeled PSMA-617
PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177Lu-Labeled PSMA-617
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DOI：
10.2967/jnumed.115.171397
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发表时间：
2016-08-01
影响因子：
9.3
通讯作者：
Haberkorn, Uwe
中科院分区：
文献类型：
--
作者：
Kratochwil, Clemens;Giesel, Frederik L.;Haberkorn, Uwe
前列腺特异性膜抗原（PSMA）是放射性核素治疗转移性去势抵抗性前列腺癌（mCRPC）的一个很好的靶点。除了高亲和力和长时间的肿瘤滞留外，dota缀合配体PSMA-617具有低肾摄取性，使其成为治疗应用的绝佳选择。我们回顾性报告了我们在对其他治疗有耐药性的mCRPC患者中使用lu -177- psma -617靶向放射性核素治疗的经验。方法：采用分子显像技术筛选psma阳性肿瘤表型患者。30例患者接受1-3个周期的Lu-177-PSMA-617治疗。在治疗期间，进行了药代动力学和放射剂量学评估。第一个周期后每2周检查一次血细胞计数，后续周期后每4周检查一次血细胞计数。每4周检测一次前列腺特异性抗原（PSA）。3个周期后再行影像学检查。结果：30例患者中有21例出现PSA应答；其中13例PSA下降超过50%。3个周期后，11例患者中有8例达到持续PSA应答（bbb50 %）超过24周，这也与放射学应答（病变数量和大小减少）相关。正常情况下，急性血液毒性较轻。弥漫性骨髓受累是更高级别骨髓抑制的危险因素，但可以通过PSMA成像提前识别。偶尔发生口干、恶心和疲劳(
Prostate-specific membrane antigen (PSMA) is an excellent target for radionuclide therapy of metastasized castration-resistant prostate cancer (mCRPC). Besides high affinity and long tumor retention, the DOTA-conjugated ligand PSMA-617 has low kidney uptake, making it an excellent choice for therapeutic application. We retrospectively report our experience with Lu-177-PSMA-617-targeted radionuclide therapy in a case series of mCRPC patients resistant to other treatments. Methods: Patients with PSMA-positive tumor phenotypes were selected by molecular imaging. Thirty patients received 1-3 cycles of Lu-177-PSMA-617. During therapy, pharmacokinetics and radiation dosimetry were evaluated. Blood cell count was checked every 2 wk after the first and every 4 wk after succeeding cycles. Prostate-specific antigen (PSA) was determined every 4 wk. Radiologic restaging was performed after 3 cycles. Results: Twenty-one of 30 patients had a PSA response; in 13 of 30 the PSA decreased more than 50%. After 3 cycles, 8 of 11 patients achieved a sustained PSA response (>50%) for over 24 wk, which also correlated with radiologic response (decreased lesion number and size). Normally, acute hematotoxicity was mild. Diffuse bone marrow involvement was a risk factor for higher grade myelosuppression but could be identified by PSMA imaging in advance. Xerostomia, nausea, and fatigue occurred sporadically (