INTRODUCTION: The mouse monoclonal antibody MOv18, directed against the alpha-isoform of folate receptor (FR), was investigated to identify the optimal radioconjugate for radioimmunotherapy of minimal residual disease in ovarian cancer. METHODS: Pharmacokinetics, biodistribution, long-term therapeutic efficacy and toxicity of MOv18, labeled with the beta-emitters (131)I, (90)Y and (177)Lu, were compared in a xenografted mouse model, composed by two cell lines, A431FR and A431MK, differing only for FR expression. RESULTS: A shorter blood clearance and a higher tumor uptake were observed for (90)Y- and (177)Lu- compared to (131)I-MOv18, and a shorter blood pharmacokinetics was recorded in A431FR-bearing animals. At equitoxic maximum tolerable doses, the general irradiation by (131)I- and (90)Y-MOv18 gives rise to strong targeted effects on A431FR and nontargeted effects on A431MK tumors, while (177)Lu-MOv18 was able to eradicate small size tumor masses expressing the antigen of interest exerting only mild non-targeted effects. CONCLUSION: (177)Lu-MOv18 at the maximal tolerated dose is the immunoradioconjugate with the best therapeutic window in experimental conditions of small tumor volume.
INTRODUCTION: The mouse monoclonal antibody MOv18, directed against the alpha-isoform of folate receptor (FR), was investigated to identify the optimal radioconjugate for radioimmunotherapy of minimal residual disease in ovarian cancer. METHODS: Pharmacokinetics, biodistribution, long-term therapeutic efficacy and toxicity of MOv18, labeled with the beta-emitters (131)I, (90)Y and (177)Lu, were compared in a xenografted mouse model, composed by two cell lines, A431FR and A431MK, differing only for FR expression. RESULTS: A shorter blood clearance and a higher tumor uptake were observed for (90)Y- and (177)Lu- compared to (131)I-MOv18, and a shorter blood pharmacokinetics was recorded in A431FR-bearing animals. At equitoxic maximum tolerable doses, the general irradiation by (131)I- and (90)Y-MOv18 gives rise to strong targeted effects on A431FR and nontargeted effects on A431MK tumors, while (177)Lu-MOv18 was able to eradicate small size tumor masses expressing the antigen of interest exerting only mild non-targeted effects. CONCLUSION: (177)Lu-MOv18 at the maximal tolerated dose is the immunoradioconjugate with the best therapeutic window in experimental conditions of small tumor volume.
Authors: Kelly Davis Orcutt; Khaled A Nasr; David G Whitehead; John V Frangioni; K Dane Wittrup Journal: Mol Imaging Biol Date: 2011-04 Impact factor: 3.488
Authors: Marc Hens; Ganesan Vaidyanathan; Xiao-Guang Zhao; Darell D Bigner; Michael R Zalutsky Journal: Nucl Med Biol Date: 2010-10 Impact factor: 2.408