The Localisation of Radiolabeled Murine Monoclonal Antibody 81C6 and its Fab Fragment in Human Glioma Xenografts in Athymic Mice

Abstract

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 tumountissue 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.

Key Words:

• Monoclonal antibody
• brain tumour
• fragment
• xenograft