PET: The Merging of Biology and Imaging into Molecular Imaging

PET and SPECT are molecular imaging techniques that use radiolabeled molecules to image molecular interactions of biological processes in vivo. PET imaging technologies have been developed to provide a pathway to the patient from the experimental paradigms of biological and pharmaceutical sciences in genetically engineered and tissue transplanted mouse models of disease. PET provides a novel way for molecular therapies and molecular diagnostics to come together in the discovery of molecules that can be used in low mass amounts to image the function of a target and, by elevating the mass, to pharmacologically modify the function of the target. In both cases, the molecules are the same or analogs of each other. PET can be used to titrate drugs to their sites of action within organ systems in vivo and to assay biological outcomes of the processes being modified in the mouse and the patient. The goal is to provide a novel way to improve the rates of discovery and approval of radiopharmaceuticals and pharmaceuticals. Extending this relationship into clinical practice can improve drug use by providing molecular diagnostics in concert with molecular therapeutics. Diseases are biological processes, and molecular imaging with PET is sensitive and informative to these processes. This sensitivity is exemplified by the detection of disease with PET without evidence of anatomic changes on CT and MRI. These biological changes are seen early in the course of disease, even in asymptomatic stages, as illustrated by the metabolic abnormalities detected with PET and FDG in Huntington's and familial Alzheimer's diseases 7 and 5 y, respectively, before symptoms appear. Differentiation of viable from nonviable tissue is fundamentally a metabolic question, as shown by the use of PET to differentiate patients with coronary artery disease who will benefit from revascularization from those who will not. Although beginning within a specific organ, cancer is a systemic disease the most devastating consequences of which result from metastases. Whole-body PET imaging with FDG enables inspection of glucose metabolism in all organ systems in a single examination to improve the detection and staging of cancer, selection of therapy, and assessment of therapeutic response. In lung and colorectal cancers, melanoma, and lymphoma, PET FDG improves the accuracy of detection and staging from 8% to 43% over conventional work-ups and results in treatment changes in 20%-40% of the patients, depending on the clinical question. Approximately 65% are upstaged because unsuspected metastases are detected, and 35% are downstaged because a structural diagnosis of lesions is changed from malignant to benign. Similar results are now being shown for other cancers. The main difference between CT, sonography, MRI, and PET or SPECT is not technologic but, rather, a difference between detecting and characterizing a disease by its anatomic features as opposed to its biology. The importance and success of developing new molecular imaging probes is increasing as PET becomes integral to the study of the integrative mammalian biology of disease and as molecular therapies targeting the biological processes of disease are developed.