The serotonin 5-HT_1A receptor has attracted wide attention as a target for treatment of psychiatric disorders. Although this receptor is important in the pharmacological mechanisms of action of new-generation antipsychotics, its characterization remains incomplete. Studies based on in vitro molecular imaging on brain tissue by autoradiography, and more recently in vivo PET imaging, have not yielded clear results, in particular due to the limitations of current 5-HT_1A radiotracers, which lack specificity and/or bind to all 5-HT_1A receptors, regardless of their functional status. The new concept of PET neuroimaging of functionally active G-protein-coupled receptors makes it possible to revisit PET brain exploration by enabling new research paradigms. For the 5-HT_1A receptor it is now possible to use [¹⁸F]-F13640, a 5-HT_1A receptor radioligand with high efficacy agonist properties, to specifically visualize and quantify functionally active receptors, and to relate this information to subjects’ pathophysiological or pharmacological state. We therefore propose imaging protocols to follow changes in the pattern of functional 5-HT_1A receptors in relation to mood deficits or cognitive processes. This could allow improved discrimination of different schizophrenia phenotypes and greater understanding of the basis of therapeutic responses to antipsychotic drugs. Finally, as well as targeting functionally active receptors to gain insights into the role of 5-HT_1A receptors, the concept can also be extended to the study of other receptors involved in the pathophysiology or therapy of psychiatric disorders.

血清素5-HT _1A受体作为治疗精神疾病的靶标已引起广泛关注。尽管该受体在新一代抗精神病药的药理作用机理中很重要，但其表征仍然不完整。基于放射自显影在脑组织上进行的体外分子成像以及最近的体内PET成像的研究尚未获得明确的结果，特别是由于当前的5-HT _1A放射性示踪剂的局限性，其缺乏特异性和/或与所有物质结合5-HT _1A受体，无论其功能状态如何。功能激活的G蛋白偶联受体的PET神经成像的新概念使通过启用新的研究范式来重新审视PET脑探索成为可能。对于5-HT _1A受体，现在可以使用[ ¹⁸ F] -F13640，一种具有高效激动剂特性的5-HT _1A受体放射性配体，专门可视化和量化功能活跃的受体，并将此信息与受试者的病理生理或药理状态。因此，我们提出了成像协议以遵循功能性5-HT _1A模式的变化与情绪低落或认知过程有关的受体。这可以改善对不同精神分裂症表型的区分，并更好地理解对抗精神病药物的治疗反应的基础。最后，除了靶向功能活性受体以了解5-HT _1A受体的作用外，该概念还可以扩展到研究与精神疾病的病理生理学或疗法有关的其他受体。