PGN650

PGN650 is a F(ab′)2 antibody fragment derived by pepsin digestion of a fully human immunoglobulin IgG1 (PGN635) that specifically targets **phosphatidylserine (PS)**, a phospholipid normally located on the inner leaflet of cell membranes, but exposed on the outer leaflet in tumor cells and tumor vasculature after oxidative stress or therapy[1][2][3][7]. Unlike intact antibodies, this fragment is smaller, potentially optimizing tumor penetration and clearance. When labeled with radioactive iodine (^124I), PGN650 can be used as a positron emission tomography (PET) imaging agent to non-invasively visualize PS exposure within the tumor microenvironment, enabling early assessment of tumor response to therapies. In preclinical models, PGN650 demonstrated selective tumor uptake, particularly after treatment with chemotherapy or irradiation, due to enhanced PS externalization. However, in first-in-human studies, tumor uptake was lower than in preclinical models, likely due to lower baseline PS exposure in patients not recently treated with cytotoxic therapies. The main indication has been as a tumor imaging and therapy response biomarker[1][2][3][7].