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 (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.

• Authors: Abraham Boskovitz, Gamal H Akabani, Charles N Pegram, Darrell D Bigner, Michael R Zalutsky
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 31 Issue 3 Pg. 345-55 (Apr 2004) ISSN: 0969-8051 [Print] United States
• PMID: 15028247 (Publication Type: Comparative Study, Evaluation Study, Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Immunoglobulin Fab Fragments
• Iodine Radioisotopes
• Radiopharmaceuticals
• Recombinant Fusion Proteins

Topics

• Animals
• Antibodies, Monoclonal (pharmacokinetics, therapeutic use)
• Body Burden
• Drug Evaluation, Preclinical
• Feasibility Studies
• Glioma (metabolism, radiotherapy)
• Humans
• Immunoglobulin Fab Fragments (metabolism, therapeutic use)
• Iodine Radioisotopes (pharmacokinetics, therapeutic use)
• Metabolic Clearance Rate
• Mice
• Mice, Nude
• Organ Specificity
• Radiation Dosage
• Radioimmunotherapy (methods)
• Radiopharmaceuticals (pharmacokinetics, therapeutic use)
• Recombinant Fusion Proteins (pharmacokinetics, therapeutic use)
• Tissue Distribution
• Tumor Cells, Cultured