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Localization of 5-HT_1A Receptors in the Living Human Brain Using [Carbonyl-¹¹C]WAY-100635: PET with Anatomic Standardization Technique

Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm, Sweden
Department of Radiology and Nuclear Medicine, Akita Research Institute of Brain and Blood Vessels, Akita City, Japan

Correspondence: For correspondence or reprints contact: Hiroshi Ito, MD, Department of Radiology and Nuclear Medicine, Akita Research Institute of Brain and Blood Vessels, 6-10 Senshu-kubota-machi, Akita City, Akita 010, Japan.

ABSTRACT

Serotonergic 5-hydroxytryptamine-1A (5-HT_1A) receptors are ofinterest in the pathophysiology of several neuropsychiatric disorderssuch as anxiety, depression and schizophrenia. [Carbonyl-¹¹C]WAY-100635has recently been shown to be suitable forquantitative determination of 5-HT_1A receptors in the human brainusing PET. For group comparisons of neuroreceptor distributionon a pixel-by-pixel basis, an anatomic standardization techniqueis required. In the current study, we have built a database ofnormal 5-HT_1A receptor distribution using [carbonyl-¹¹C]WAY-100635and an anatomic standardization technique. Methods: APET examination lasting 63 min was performed on six subjectsafter intravenous injection of [carbonyl-¹¹C]WAY-100635. Theradioactivity of the PET images were integrated in the interval12–63 min and normalized by the radioactivity of the cerebellum,providing a measure of the binding potential (BP) in each pixel.Each PET image was transformed into a standard brain anatomyusing a computerized brain atlas system. From the standardizedPET images, the sample mean and the SD of the BP werecalculated in each pixel. Results: On the anatomically standardizedaverage image, high BP was observed in the cerebralcortices, hippocampus and raphe nucleus, whereas low BP wasobserved in the basal ganglia and thalamus. This regionaldistribution is in good agreement with the distribution of 5-HT_1Areceptors known from in vitro studies. Conclusion: The anatomicstandardization technique permits building of a database ofthe normal 5-HT_1A receptor distribution in the living human brain.This technique can be applied for group comparisons of neuroreceptordistribution on a pixel-by-pixel basis.

Key Words: serotonin 5-HT_1A receptor • brain • WAY-100635 • PET • anatomic standardization

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