A novel immunoscintigraphy technique using metabolizable linker with angiotensin II treatment

Abstract

Immunoscintigraphy is a tumour imaging technique that can have specificity, but high background radioactivity makes it difficult to obtain tumour imaging soon after the injection of radioconjugate. The aim of this study is to see whether clear tumour images can be obtained soon after injection of a radiolabelled reagent using a new linker with antibody fragments (Fab), in conditions of induced hypertension in mice. Fab fragments of a murine monoclonal antibody against human osteosarcoma were labelled with radioiodinated 3'-iodohippuryl N-epsilon-maleoyl-L-lysine (HML) and were injected intravenously to tumour-bearing mice. Angiotensin II was administered for 4 h before and for 1 h after the injection of radiolabelled Fab. Kidney uptake of 125I-labelled-HML-Fab was much lower than that of 125I-labelled-Fab radioiodinated by the chloramine-T method, and the radioactivity of tumour was increased approximately two-fold by angiotensin II treatment at 3 h after injection, indicating high tumour-to-normal tissue ratios. A clear tumour image was obtained with 131I-labelled-HML-Fab at 3 h post-injection. The use of HML as a radiolabelling reagent, combined with angiotensin II treatment, efficiently improved tumour targeting and enabled the imaging of tumours. These results suggest the feasibility of PET scan using antibody fragment labelled with 18F-fluorine substitute for radioiodine.