An advanced paradigm for molecular imaging and radionuclide therapy of cancer

We are on the brink of a new, advanced paradigm of detection, diagnosis, characterization and therapy in oncology that will provide far better patient outcomes, with far less morbidity and mortality. This paradigm utilizes positron-emitting tracers for imaging malignancies with PET/CT to diagnose, stage and characterize various tumors, including clonal variations. Imaging will take into account the hallmarks of cancer, as described by Hanahan and Weinberg. Especially important will be evaluation of tumor angiogenesis, evading immune detection and destruction, evading growth suppressors and apoptosis, reprogramming of energy metabolism and tissue invasion and metastasis. Another feature of cancer cells to evaluate will be the tumor microenvironment. In addition to standard imaging with F-18 FDG to evaluate glucose metabolism, a number of novel PET tracers will be used, such as tracers to evaluate proliferation (DNA synthesis), evaluation of amino acid metabolism, such as F-18 glutamine, evaluation of various cell-surface receptors, evaluation of tumor angiogenesis and hypoxia, and evaluation of clonal variations. Tracers targeting osteoclastic activity may be useful. Advanced versions of PERCIST criteria will be utilized to evaluate the metabolic response to therapy. These studies will provide solid evidence of efficacy, quality and value, and will become incorporated into clinical guidelines, such as NCCN. [Cancers will be classified by molecular phenotypes, and the site of origin will become secondary. Molecular phenotypes will be determined by molecular pathology and various molecular imaging studies using highly specific tracers. - Richard Baum, MD] Once a malignancy is fully characterized, we can utilize radionuclide therapies, most likely in various combinations of alpha- and beta-emitters, many as theranostic pairs, and probably in combination with other modalities, such as immune modulation, radiation therapy, chemotherapy or viral therapy. Treatment will be specifically targeted against each malignancy. These therapies will identify and disrupt various enzymatic pathways, as well as signaling pathways and chemical mediators. These therapies will also rely on precise dosimetry. It will likely be beneficial for patients to receive whole body radiation from Radiation Oncology for immune stimulation prior to initiation of these radionuclide therapies. These therapies will disrupt the tumor microenvironment, which includes the tumor support structure an