Clinical experience with α-particle-emitting 211At:: Treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6
Clinical experience with α-particle-emitting 211At:: Treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6
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DOI：
10.2967/jnumed.107.046938
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发表时间：
2008-01-01
影响因子：
9.3
通讯作者：
Bigner, Darell D.
中科院分区：
文献类型：
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作者：
Zalutsky, Michael R.;Reardon, David A.;Bigner, Darell D.
α-粒子发射放射性核素，如At-211，半衰期为7.2小时，可能最适合于战略敏感肿瘤部位的分子靶向放射治疗，如中枢神经系统中的那些。由于α粒子的射程比β粒子短得多且细胞毒性更强，At-211标记的试剂可能是根除恶性脑肿瘤手术减积后剩余肿瘤细胞的理想选择。本研究的主要目的是探讨这种方法在复发性恶性脑肿瘤患者中的可行性和安全性。研究方法：嵌合抗腱生蛋白单克隆抗体81 C6（ch 81 C6）（10 mg）通过使用N-琥珀酰亚胺基3-[At-211]阿司他苯甲酸酯用71-347 MBq的At-211标记。18例患者接受了At-211标记的ch 81 C6（At-211-ch 81 C6）给药至手术创建的切除腔（SCRC），然后接受挽救化疗。进行连续伽马相机成像和24小时内的血液采样。结果：在SCRC中发生了总计96.7% +/- 3.6%（平均值+/- SD）的At-211衰变，平均血池百分比注射剂量为
alpha-Particle-emitting radionuclides, such as At-211, with a 7.2-h half-life, may be optimally suited for the molecularly targeted radiotherapy of strategically sensitive tumor sites, such as those in the central nervous system. Because of the much shorter range and more potent cytotoxicity of a-particles than of beta-particles, At-211-labeled agents may be ideal for the eradication of tumor cells remaining after surgical debulking of malignant brain tumors. The main goal of this study was to investigate the feasibility and safety of this approach in patients with recurrent malignant brain tumors. Methods: Chimeric antitenascin monoclonal antibody 81C6 (ch81C6) (10 mg) was labeled with 71-347 MBq of At-211 by use of N-succinimidyl 3-[At-211]astatobenzoate. Eighteen patients were treated with At-211-labeled ch81C6 (At-211-ch81C6) administered into a surgically created resection cavity (SCRC) and then with salvage chemotherapy. Serial gamma-camera imaging and blood sampling over 24 h were performed. Results: A total of 96.7% +/- 3.6% (mean +/- SD) of At-211 decays occurred in the SCRC, and the mean blood-pool percentage injected dose was