Pancreatic cancer remains one of the most lethal of cancers, due to a lack of effective detection methods, complex and invasive surgical treatments, and early spread and metastasis. Better therapeutic approaches are needed, along with improved means for detecting and staging pancreatic cancer. Prostate stem cell antigen (PSCA), originally identified as a marker in prostate cancer, is highly over expressed in pancreatic adenocarcinoma. Antibodies recognizing PSCA are currently in clinical evaluation for treatment of pancreatic cancer. A humanized, affinity-matured anti-PSCA engineered antibody fragment (minibody;single-chain Fv-CH3, 80 kDa) has demonstrated rapid tumor targeting and blood clearance optimized for imaging applications. The goal of this Phase I SBIR proposal is to expand these preliminary studies to include production and evaluation of a set of anti-PSCA minibodies as well as anti-PSCA cysdiabodies (single-chain Fv dimer, 50 kDa), a smaller format with additional, complementary advantages. A high expressing variant of each will be selected for protein production, radiolabeling with 1240I and evaluation of biodistribution, tumor targeting, and microPET imaging in a preclinical model of pancreatic cancer. Based on performance (tumore uptake, blood clearance, contrast, optimal imaging time), a lead PSCA-specific imaging agent will be selected for sale-up towards clinical development in Phase II).
