Positron emission tomography and single-photon emission computed tomography in central nervous system drug development.
In this review, the value of functional imaging [positron emission tomography (PET)/single-photon emission computed tomography (SPECT)] in drug development is considered. Radionuclide imaging can help establish the diagnosis of neurodegenerative disorders where this is in doubt and provides a potential biomarker for following drug effects on disease progression. PET and SPECT can help understand mechanisms of disease and determine the functional effects of therapeutic approaches on neurotransmission and metabolism. Synthesizing radiotracer analogs of novel drugs can provide proof of principle that these agents reach their enzyme or receptor targets and delineate their regional brain distribution. If such radiotracers do not prove to have ideal properties for imaging, the concept of microdosing potentially allows multiple other drug analogs to be tested with less stringent regulatory requirements than for novel medicinals. Finally, PET tracers can provide receptor and enzyme active site dose occupancy profiles, thereby guiding dosage selection for phase 1 and phase 2 trials. The eventual hope is that radiotracer imaging will provide a surrogate marker for drug efficacy, although this has yet to be realized, and progress the concept of personalized medicine where receptor/enzyme binding profiles help predict therapeutic outcome.
Brooks
David J
DJ
Medical Research Council Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, London W12 0NN, United Kingdom. david.brooks@csc.mrc.ac.uk
D000818:Animals; D002491:Central Nervous System Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009422:Nervous System Diseases / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography; D015899:Tomography, Emission-Computed, Single-Photon
D002491:Central Nervous System Agents