Human/murine chimeric 81C6 F(ab′) 2 fragment: preclinical evaluation of a potential construct for the targeted radiotherapy of malignant glioma

Abstract

We have obtained encouraging responses in recent Phase I studies evaluating 131I-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-[ 131I]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 131I-labeled ch81C6 F(ab′) 2 may warrant further evaluation as a targeted radiotherapeutic for the treatment of brain tumors.