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Journal Article
Review
PET technology for drug development in psychiatry.
Neuropsychopharmacology Reports 2020 May 29
Positron emission tomography (PET) is a non-invasive imaging method to measure the molecule in vivo. PET imaging can evaluate the central nervous system drugs as target engagement in the human brain. For antipsychotic drugs, adequate dopamine D2 receptor occupancy ("therapeutic window") is reported to be from 65%-70% to 80% to achieve the antipsychotic effect without extrapyramidal symptoms. For antidepressants, the clinical threshold of serotonin transporter (5-HTT) occupancy is reported to be 70%-80% although the relation between the side effect and 5-HTT occupancy has not yet been established. Evaluation of norepinephrine transporter (NET) occupancy for antidepressant is ongoing as adequate PET radioligands for NET were developed recently. Measurement of the target occupancy has been a key element to evaluate the in vivo target engagement of the drugs. In order to evaluate new drug targets for disease conditions such as negative symptoms/cognitive impairment of schizophrenia and treatment-resistant depression, new PET radioligands need to be developed concurrently with the drug development.
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