Center for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden.
Takeda Development Center Japan, Takeda Pharmaceutical Company Limited, Osaka, Japan.
Neuropsychopharmacol Rep. 2020 Jun;40(2):114-121. doi: 10.1002/npr2.12084. Epub 2020 May 28.
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.
正电子发射断层扫描（PET）是一种非侵入性的成像方法，用于测量体内的分子。PET 成像可评估中枢神经系统药物作为人类大脑中的靶点结合。对于抗精神病药物，据报道，充分的多巴胺 D2 受体占有率（“治疗窗口”）为 65%-70%至 80%，以实现抗精神病作用而无锥体外系症状。对于抗抑郁药，据报道，5-羟色胺转运体（5-HTT）占有率的临床阈值为 70%-80%，尽管副作用与 5-HTT 占有率之间的关系尚未建立。最近开发了用于 NET 的适当 PET 放射性配体，正在对去甲肾上腺素转运体（NET）占有率进行评估。对目标占有率的测量一直是评估药物体内目标结合的关键要素。为了评估疾病状况（如精神分裂症的阴性症状/认知障碍和治疗抵抗性抑郁症）的新药物靶点，需要与药物开发同时开发新的 PET 放射性配体。
