211At-AntiCD33 in NMRI nu/nu mice

Summary The aim of this study is to verify the in vivo stability, to determine the biodistribution and to estimate the unspecific radiotoxicity of an 211At-labelled CD33-antibody (211At-anti-CD33) in mice with a view to therapeutic application in treating leukaemia. Animals, methods: 211At was produced via the 209Bi(α,2n)211At reaction and was linked via 3-211At-succinimidyl-benzoate to the anti-CD33-antibody. The biodistribution and the in vivo stability in serum were determined after i.v.-injection in NMRI nu/nu-mice. For toxicity experiments, mice received either three times 315–650 kBq 211At-antiCD33 or unlabelled antibody and NaCl-solution respectively. Results: 211At-antiCD33 showed a characteristic biodistribution complying with the unspecific antibody retention in the reticular endothelial system. The largest proportion of radioactivity remained in blood and blood-rich tissues with a minor accumulation in the thyroid and stomach. After 21 h, > 85% of activity in serum still represented intact antibody. Mice showed no difference in unspecific toxicity of 211At-labelled antibodies over six months compared to those treated with unlabelled antibody and NaCl-solution respectively, with regard to histopathologic lesions, survival time, behaviour and haemograms. Conclusion: The radiolabelling method yielded adequate in vivo stability of 211At-antiCD33. Biodistribution with rapid elimination of free 211At via kidneys and urine complies with requirements for targeted therapy. Activity doses potentially required for treatment do not elicit radiotoxicity to normal organs in mice. Further development is required to enhance the apparent specific activity and to verify the efficacy in an adequate animal model before phase I clinical studies in leukaemia can be envisaged.