Rapid imaging of human melanoma xenografts using an scFv fragment of the human monoclonal antibody H11 labelled with In-111

H11 is a human IgM monoclonal antibody which recognizes a novel tumour-asso ciated antigen expressed on melanoma, glioma, breast cancer, colon cancer, prostate cancer, lung cancer and B-cell lymphoma. In this study, a recombin ant single-chain Fv (scFv) fragment of H11 labelled with In-111 was investi gated for tumour imaging in athymic mice implanted subcutaneously with A-37 5 human melanoma xenografts. H11 scFv was derivatized with diethylenetriami nepentaacetic acid (DTPA) for labelling with 111In. The immunoreactivity of DTPA-H11 scFv against A-375 cells in vitro ranged from 23% to 36%. In-111- DTPA-H11 scFv was rapidly eliminated from the blood and most normal tissues (except the kidneys) reaching maximum tumour/blood ratios of 12:1 at 48 h post-injection. Tumours were imaged as early as 40 min after injection. The kidneys accumulated the highest concentration of radioactivity (up to 185% injected dose/g). Tumour uptake was 1-3% injected dose/g. The whole-body r adiation absorbed dose predicted for administration of 185 MBq of In-111-DT PA-H11 scFv to humans was 37 mSv. The radiation absorbed dose estimates for the kidneys, spleen and intestines were 405 mSv, 698 mSv and 412 mSv, resp ectively The results of this preclinical study and a concurrent phase I tri al suggest a promising role for H11 scFv for tumour imaging. ((C) 2001 Lipp incott Williams & Wilkins).