Boskovitz Abraham, Akabani Gamal H, Pegram Charles N, Bigner Darrell D, Zalutsky Michael R
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Nucl Med Biol. 2004 Apr;31(3):345-55. doi: 10.1016/j.nucmedbio.2003.10.008.
We have obtained encouraging responses in recent Phase I studies evaluating (131)I-labeled human/murine chimeric 81C6 anti-tenascin monoclonal antibody (ch81C6) administered into surgically-created tumor resection cavities in brain tumor patients. However, because the blood clearance is slow, hematologic toxicity has been higher than seen with murine 81C6 (mu81C6). In the current study, a series of paired-label experiments were performed in athymic mice bearing subcutaneous D-245 MG human glioma xenografts to compare the biodistribution of the fragment ch81C6 F(ab')(2) labeled using Iodogen to a) intact ch81C6, b) mu81C6, and c) ch81C6 F(ab')(2) labeled using N-succinimidyl 3-[(131)I]iodobenzoate. Tumor retention of radioiodine activity for the F(ab')(2) fragment was comparable to that for intact ch81C6 for the first 24 h and to that for mu81C6 for the first 48 h; as expected, blood and other normal tissue levels declined faster for ch81C6 F(ab')(2.) Radiation dosimetry calculations suggest that (131)I-labeled ch81C6 F(ab')(2) may warrant further evaluation as a targeted radiotherapeutic for the treatment of brain tumors.
在近期的I期研究中，我们将（131）I标记的人/鼠嵌合81C6抗腱生蛋白单克隆抗体（ch81C6）注入脑肿瘤患者手术形成的肿瘤切除腔内，已获得令人鼓舞的反应。然而，由于血液清除缓慢，血液学毒性高于鼠源81C6（mu81C6）。在本研究中，对携带皮下D - 245 MG人胶质瘤异种移植物的无胸腺小鼠进行了一系列配对标记实验，以比较用Iodogen标记的片段ch81C6 F(ab')(2)与a）完整的ch81C6、b）mu81C6和c）用N - 琥珀酰亚胺基3 - [(131)I]碘苯甲酸酯标记的ch81C6 F(ab')(2)的生物分布。F(ab')(2)片段的放射性碘活性在肿瘤中的保留情况在最初24小时与完整的ch81C6相当，在最初48小时与mu81C6相当；正如预期的那样，ch81C6 F(ab')(2)的血液和其他正常组织水平下降得更快。放射剂量学计算表明，（131）I标记的ch81C6 F(ab')(2)作为脑肿瘤的靶向放射治疗药物可能值得进一步评估。
