Minibody Imaging Of Prostate-Specific Membrane Antigen (Psma): From Concept In Clinic.

e16057 Background: PSMA is an ideal target for imaging prostate cancer as it is highly expressed in a majority of lesions with low expression in normal prostate epithelium. This study describes the preclinical development of 89Zr-Df-IAB2M, an anti-PSMA minibody (Mb) conjugated with desferrioxamine (Df) and radiolabeled with 89Zr for imaging primary prostate cancer and soft tissue and bone metastases. Methods: In vitro binding analyses of IAB2M, an 80 kDa humanized Mb, included flow cytometry and ELISA. Serial PET imaging, tumor targeting, pharmacokinetics (PK) and tissue biodistribution of 89Zr-Df-IAB2M were evaluated in athymic male mice bearing 22Rv1 (PSMA+) and PC3 (PSMA-) subcutaneous tumors. Organ dosimetry was determined from PET scans of non-tumor bearing mice at 4, 24 and 48 h. A GLP toxicokinetic study evaluated two consecutive 10 and 25 mg/kg doses. Results: IAB2M, Df-IAB2M and Zr-Df-IAB2M bound to cell surface PSMA with high affinity (~0.06 nM). 89Zr-Df-IAB2M retained high (u003e90%) immunoreactivi...