In vivo studies of pharmacokinetics and efficacy of bismuth-213 labeled antimelanoma monoclonal antibody 9.2.27

Abstract

Objectives Key objectives of the study were to determine the pharmacokinetics and efficacy of the alpha emitting Bismuth- 213 labeled 9.2.27 alpha-immunoconjugate (AIC). Methods Balb/c nude mice were injected with varying doses of AIC to determine the pharmacokinetics of the AIC. The results were normalized to percent counts per minute (CPM) per gram per 3.7 MBq of the AIC (%CPM/g/3.7MBq) for each organ. Efficacy was determined by injected varying doses of AIC to different stages of tumour growth for intra-lesional, systemic and multiple dose TAT. Results Biodistribution studies showed similar pharmacokinetics for blood and brain, liver, kidneys, spleen, gut, heart, lungs and bone marrow, indicating that there was no retention of AIC. This is particularly important for brain (due to the presence of NG2+ cells) as the antibody 9.2.27 may reach NG2 positive cells. Tumour growth at 2-days post-inoculation was completely inhibited by TAT. The response to TAT was inversely proportional to tumour growth, i.e. a reduction in response was observed with increased tumour burden. A multiple dose regime was found to be more effective than single dose. Conclusions TAT is effective for the treatment of micrometastatic melanoma, when the tumour is preangiogenic in the form of isolated cells or cell clusters. There is no evidence of retention of AIC in brain, kidneys and other vital organs.