177Lu- labeled MOv18 as compared to 131I- or 90Y-labeled MOv18 has the better therapeutic effect in eradication of alpha folate receptor-expressing tumor xenografts

IntroductionThe mouse monoclonal antibody MOv18, directed against the α-isoform of folate receptor (FR), was investigated to identify the optimal radioconjugate for radioimmunotherapy of minimal residual disease in ovarian cancer.MethodsPharmacokinetics, biodistribution, long-term therapeutic efficacy and toxicity of MOv18, labeled with the beta-emitters 131I, 90Y and 177Lu, were compared in a xenografted mouse model, composed by two cell lines, A431FR and A431MK, differing only for FR expression.ResultsA shorter blood clearance and a higher tumor uptake were observed for 90Y- and 177Lu- compared to 131I-MOv18, and a shorter blood pharmacokinetics was recorded in A431FR-bearing animals. At equitoxic maximum tolerable doses, the general irradiation by 131I- and 90Y-MOv18 gives rise to strong targeted effects on A431FR and nontargeted effects on A431MK tumors, while 177Lu-MOv18 was able to eradicate small size tumor masses expressing the antigen of interest exerting only mild non-targeted effects.Conclusion177Lu-MOv18 at the maximal tolerated dose is the immunoradioconjugate with the best therapeutic window in experimental conditions of small tumor volume.