Targeting metastatic prostate cancer with radiolabeled monoclonal antibody J591 to the extracellular domain of prostate specific membrane antigen
Targeting metastatic prostate cancer with radiolabeled monoclonal antibody J591 to the extracellular domain of prostate specific membrane antigen
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DOI：
10.1097/01.ju.0000091655.77601.0c
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发表时间：
2003-11-01
影响因子：
6.6
通讯作者：
Goldsmith, SJ
中科院分区：
文献类型：
--
作者：
Bander, NH;Trabulsi, EJ;Goldsmith, SJ
目的：我们对2项I期放射免疫治疗试验中收集的成像数据进行了中期分析，以确定针对前列腺特异性膜抗原（PSMA）胞外结构域的单克隆抗体（mAb）J591准确靶向已知转移性前列腺癌部位的能力。材料与方法：患有进展性激素非依赖性前列腺癌的患者进入2项放射性标记mAb J591的I期剂量探索试验。J591是第一种靶向PSMA细胞外结构域的mAb，也是第一种在人体中测试的针对PSMA的去免疫化（人源化）mAb。这些试验主要用于评估剂量限制性毒性、最大耐受剂量、药代动力学和器官剂量测定。对前53例患者的平面伽马相机成像研究进行了审查，并与传统成像研究（包括骨扫描、计算机断层扫描和/或磁共振成像）显示的转移性前列腺癌部位进行了比较。在1项试验中，29名患者接受了（111）铟-J591成像，随后接受（90）钇-J591治疗。在平行试验中，24例患者接受了（177）镥-J591，一种同位素，可以直接imaged.Results：回顾53例患者46（87%）有转移性疾病的证据，在常规扫描。总体而言，在43例可评价患者中，J591准确靶向了42例（98%）骨和/或软组织病变。J591准确地针对骨病变32 34（94%）和软组织病变13 18（72%）evaluablepatients.Conclusions：放射性标记的J591准确地针对骨和软组织转移性前列腺癌的网站，并可能是有用的针对治疗和/或诊断显像剂。
Purpose: We performed an interim analysis of imaging data collected in 2 phase I radioimmunotherapy trials to determine the ability of monoclonal antibody (mAb) J591 directed to the extracellular domain of prostate specific membrane antigen (PSMA) to target sites of known metastatic prostate cancer accurately. Materials andMethods: Patients with progressing hormone independent prostate cancer were entered in 2 phase I dose finding trials with radiolabeled mAb J591. J591 is the first mAb targeting the extracellular domain of PSMA as well as the first de-immunized (humanized) mAb to PSMA to be tested in humans. These trials were primarily designed to assess dose limiting toxicity, maximum tolerated dose, pharmacokinetics and organ dosimetry. Planar gamma camera imaging studies obtained on the first 53 patients were reviewed and compared to sites of metastatic prostate cancer visualized on conventional imaging studies including bone scan, computerized tomography and/or magnetic resonance imaging. In 1 trial 29 patients received (111)indium-J591 for imaging followed by (90)yttrium-J591 for therapy. In the parallel trial 24 patients were treated with (177)lutetium-J591, an isotope that can be imaged directly.Results: Of 53 patients reviewed 46 (87%) had evidence of metastatic disease on conventional scans. Overall, of the 43 evaluable patients J591 accurately targeted bone and/or soft tissue lesions in 42 (98%). J591 accurately targeted bone lesions in 32 of 34 (94%) and soft tissue lesions in 13 of 18 (72%) evaluable patients.Conclusions: Radiolabeled J591 accurately targets bone and soft tissue metastatic prostate cancer sites, and may be useful for targeting therapeutic and/or diagnostic imaging agents.