In Vivo Biodistribution, PET Imaging, and Tumor Accumulation of 86Y- and 111In-Antimindin/RG-1, Engineered Antibody Fragments in LNCaP Tumor–Bearing Nude Mice

To optimize in vivo tissue uptake kinetics and clearance of engineered monoclonal antibody (mAb) fragments for radiother-apeutic and radiodiagnostic applications, we compared the bio-distribution and tumor localization of four 111In- and 86Y-labeled antibody formats, derived from a single antimindin/RG-1 mAb, in a prostate tumor model. The IgG, diabody, single-chain variable domain (scFv), and novelminiantibody formats, composed of the human IgE-CH4 and a modified IgG1 hinge linked to scFv do-mains, were compared. Methods: Antibodies were first deriva-tized with the bifunctional chelator CHX-A$-diethylenetriamine pentaacetic acid and then bound to the radiometal to create ra-diolabeled immunoconjugates. Human LNCaP xenografts were grown in nude mice, and 111In- or 86Y-labeled antibodies were administered intravenously. Tissues were harvested at different times, and the level of antibody deposition was determined b