[Strategy for development of imaging biomarkers].
Imaging biomarkers are getting to be more and more important to measure physiological and biological functions, to evaluate higher brain function, to study the pathophysiology of various disorders and to develop effective therapeutic drugs. Positron emission tomography (PET) and single-photon emission computed tomography are representative molecular imaging methods. Development of radiopharmaceuticals is a key for successful in vivo imaging. So far many radioligands have been developed for PET and applied to clinical studies. Development of radioligands has the following process: 1) selection of biomarkers, 2) selection of leading compounds, radionuclide, labeled position, and synthesis methods, 3) in vitro and in vivo evaluation including probability for imaging, selectivity, specificity, and species differences, and 4) evaluation of safety such as acute toxicity, mutagenicity and radiation dosimetry. Clinically, first PET studies were performed in normal subjects, and then recently, radiation dosimetry has been measured directly by dynamic whole body scans. Second PET studies are applied to patients with various disorders. In this manuscript, the author introduces experiences and concepts for development of radioligands for studying the central nervous system.
Ishiwata
Kiichi
K
Positron Medical Center, Tokyo Metropolitan Institute for Gerontology, 1-1 Naka-cho, Itabashi-ku, Tokyo, 173-0022 Japan. ishiwata@pet.tmig.or.jp
D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000378:metabolism; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D008024:Ligands; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D018047:Receptors, Purinergic P1; D017480:Receptors, sigma; D011984:Sensory Receptor Cells; D013045:Species Specificity; D015899:Tomography, Emission-Computed, Single-Photon
D015415:Biomarkers; D008024:Ligands; D019275:Radiopharmaceuticals; D018047:Receptors, Purinergic P1; D017480:Receptors, sigma