Applications of positron emission tomography in animal models of neurological and neuropsychiatric disorders

Positron emission tomography (PET) provides dynamic images of the biodistribution of radioactive tracers in the brain. Through application of the principles of compartmental analysis, tracer uptake can be quantified in terms of specific physiological processes such as cerebral blood flow, cerebral metabolic rate, and the availability of receptors in brain. Whereas early PET studies in animal models of brain diseases were hampered by the limited spatial resolution of PET instruments, dedicated small-animal instruments now provide molecular images of rodent brain with resolution approaching 1mm, the theoretic limit of the method. Major applications of PET for brain research have consisted of studies of animal models of neurological disorders, notably Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD), stroke, epilepsy and traumatic brain injury; these studies have particularly benefited from selective neurochemical lesion models (PD), and also transgenic rodent models (AD, HD). Due to their complex and uncertain pathophysiologies, corresponding models of neuropsychiatric disorders have proven more difficult to establish. Historically, there has been an emphasis on PET studies of dopamine transmission, as assessed with a range of tracers targeting dopamine synthesis, plasma membrane transporters, and receptor binding sites. However, notable recent breakthroughs in molecular imaging include the development of greatly improved tracers for subtypes of serotonin, cannabinoid, and metabotropic glutamate receptors, as well as noradrenaline transporters, amyloid-β and neuroinflammatory changes. This article reviews the considerable recent progress in preclinical PET and discusses applications relevant to a number of neurological and neuropsychiatric disorders in humans.