Immuno-Positron Emission Tomography

This chapter provides general information about monoclonal antibodies (MAb)-targeted diagnosis and therapy of cancer as well as about positron emission tomography (PET), PET systems, and quantification. Eight MAbs have been approved for treatment of cancer. Five of these MAbs have been approved for treatment of hematologic malignancies: rituximab, gemtuzumab ozogamicin, alemtuzumab, ibritumomab tiuxetan, and tositumomab. Three MAbs are approved for therapy of solid tumors: trastuzumab for treatment of metastatic breast cancer and cetuximab and bevacizumab for treatment of metastatic colorectal cancer. Most of these are unmodified MAbs and can act by mediating antibody-dependent cellular cytotoxicity (ADCC) or complement-depending cytotoxicity (CDC), by apoptosis induction, or by interfering with signal transduction pathways. Immuno-PET is based on annihilation coincidence detection after labeling of a MAb or MAb fragment with a positron-emitting radionuclide. The emitted positron travels a distance of a few millimeters, depending on the initial positron energy and the density of the surroundings. After having lost its kinetic energy, combining with an electron leads to the so-called annihilation process, yielding two photons each with energy of 511 keV emitted simultaneously in opposite directions. After administration of a PET conjugate to a patient, the distribution of the compound is monitored by detection of the annihilation photon pairs with a PET camera. For a positron emitter to be appropriate for immuno-PET, it has to fulfill several requirements such as the positron emitter should have appropriate decay characteristics for optimal resolution and optimal quantitative accuracy, its production should be easy and cheap, and it should be possible to achieve easy and stable coupling to MAbs with maintenance of the antibody's in vivo biodistribution characteristics.