Multifunctional PSCA Antibody Fragments for PET and Optical Prostate Cancer Imaging

The goals of this funding were to develop and evaluate universal optimized cys-diabody and cys-minibody fragments against prostate stem cell antigen PSCA for PET imaging of prostate cancer. During the three-year project period, we developed and produced a novel anti-PSCA cys-minibody and employed it for singly- and dually-labeled PET or PEToptical imaging in mouse models of prostate cancer. In addition, focusing on the smaller anti-PSCA cys-diabody, we demonstrated dual labeling and imaging in models of pancreatic cancer, which also express PSCA. Novel linker chemistry was developed to attach both fluorescent labels and F-18 in a single moiety. This tag, fluorescently labeled, was site-specifically conjugated to the anti-PSCA cys-diabody and rapidly labeled with F-18 using click chemistry. Successful sequential microPET and optical imaging were demonstrated in mouse models. As all these agents are based on a fully humanized antibody, they would be suitable for clinical translation.