The localisation of radiolabelled murine monoclonal antibody 81C6 and its Fab fragment in human glioma xenografts in athymic mice

• Published in: British journal of neurosurgery Vol. 2; no. 2; p. 179
• Main Authors: Colapinto, E V, Lee, Y S, Humphrey, P A, Zalutsky, M R, Friedman, H S, Bullard, D E, Bigner, D D
• Format: Journal Article
• Language: English
• Published: England 1988
• Subjects: Animals; Antibodies, Monoclonal - pharmacokinetics; Brain Neoplasms - immunology; Brain Neoplasms - radiotherapy; Glioma - immunology; Glioma - radiotherapy; Humans; Immunoglobulin Fab Fragments - pharmacokinetics; Mice; Mice, Nude - immunology; Neoplasm Transplantation; Radiation Dosage; Radiotherapy - methods; Transplantation, Heterologous
• ISSN: 0268-8697

The localisation of the radioiodinated Fab fragment of monoclonal antibody (Mab) 81C6, reactive with a glioma-associated extracellular matrix antigen, was studied in athymic mice bearing subcutaneous and intracranial xenografts of D-54 MG glioma cells. In vitro 81C6 Fab showed a marked loss of immunoreactivity and affinity for antigen compared to intact Mab 81C6. In vivo, the plasma half-life of 81C6 Fab was 7.0 hours compared to 2.1 days for 81C6. 81C6 Fab levels in tumours peaked at 2.6-3.8% injected dose/g in 2-6 h; Mab 81C6 reached 33.9% dose/g at 48 h. Localisation indices and tumour:tissue ratios were superior for Mab 81C6. Estimated radiation doses to tumour and normal tissues were lower for 131I-81C6 Fab than 131I-81C6. To realise the theoretical benefits of fragments as localising agents, Fab fragments of higher immunoreactivity and affinity, or bivalent F(ab')2 fragments are required.