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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Boskovitz, A; Akabani, GH; Pegram, CN; Bigner, DD; Zalutsky, MR

Published Date

  • April 2004

Published In

Volume / Issue

  • 31 / 3

Start / End Page

  • 345 - 355

PubMed ID

  • 15028247

Pubmed Central ID

  • 15028247

Electronic International Standard Serial Number (EISSN)

  • 1872-9614

International Standard Serial Number (ISSN)

  • 0969-8051

Digital Object Identifier (DOI)

  • 10.1016/j.nucmedbio.2003.10.008

Language

  • eng