Preclinical PET imaging of antibody therapies for cancer

Monoclonal antibodies have become important in the systemic treatment of cancer. They are applied in different ways. Among antibodies, the immune checkpoint inhibitors now play a clear role by activating the immune system. Antibodies can also be charged with a cytotoxic or radioactive payload. The antibody-drug conjugates (ADCs) are obtaining a firm role in treating patients with cancer. And increasingly studies are ongoing with antibodies radiolabeled with beta- (especially lutetium-177) and alpha-emitting radionuclides. For so-called targeted alpha therapy, alpha particle emitting radionuclides, e.g., thorium-227(227Th), or actinium-225 (225Ac) are coupled to tumor-targeting monoclonal antibodies. As for all systemic treatments, treatment with antibodies does not benefit all patients. It may help to understand the whole-body behavior of these antibodies, shedding light on their unique target-mediated distribution and heterogeneous tumor-targeting. Positron emission tomography (PET) could visualize whole-body distribution, noninvasively, of zirconium-89 (89Zr) labeled antibody therapies. Access to therapeutic antibodies is globally limited because they are expensive. The availability and use of monoclonal antibody biosimilars could potentially retain the healthcare costs of these expensive drugs. The research in this thesis focussed on monoclonal antibodies and aiming to identify challenges for monoclonal antibody biosimilars in cancer and explore preclinical 89Zr PET imaging of antibody therapies to evaluate their in vivo behavior, e.g., biodistribution, tumor uptake, and pharmacodynamics