Tools & Technologies for Human Functional Neuroimaging: Molecular Imaging of Drug
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Manabu TASHIRO, Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope center,
Tohoku University
Functional and molecular imaging is a new multidisciplinary field that enables the visualizationof the cellular function and disease processes at molecular level in living organisms withoutperturbing them. The research outputs are applicable to diagnosis of diseases such as cancer,
neurological and cardiovascular diseases. We have been conducting a variety of research projects
such as development and clinical evaluation of new tracers, elucidation of the pathologicalmechanism of various neurological diseases and stress disorders, as well as new studies forhealthy-promotion sciences, mainly using positron emission tomography (PET). In this introductorytalk, methodological information for functional neuroimaging in humans will be presented.
As an example of molecular imaging research in humans, PET studies on drug actions will bepresented. Histamine H1 antagonists, or antihistamines, are often prescribed for treatment of allergic
disorders. The antihistamines, sometimes induce sleepiness and cognitive deficits in allergic patients.
Mechanism of the CNS side effects has been understood as blockade of neural transmission via
histamine H1 receptors (H1R) in the brain. PET measurement has been useful to classify new
antihistamines into sedative, minimally-sedative, and non-sedative drugs based on their H1R
occupancy values measured by PET with [11C]doxepin. Recently, this technique has been applied
further to other drugs such as antidepressants and antipsychotics.
References
Brain histamine H1 receptor occupancy measured by PET after oral administration of levocetirizine, anon-sedating antihistamine. Expert Opin Drug Saf. 2015 Feb;14(2):199-206.
Histamine H ₁ receptor occupancy by the new-generation antidepressants fluvoxamine andmirtazapine: a positron emission tomography study in healthy volunteers. Psychopharmacology (Berl).
2013 Nov;230(2):227-34.
Next-day residual sedative effect after nighttime administration of an over-the-counter antihistamine
sleep aid, diphenhydramine, measured by positron emission tomography. J Clin Psychopharmacol. 2010
Dec;30(6):694-701.
Dose dependency of brain histamine H(1) receptor occupancy following oral administration of cetirizinehydrochloride measured using PET with [11C]doxepin. Hum Psychopharmacol. 2009 Oct;24(7):540-8.
Brain histamine H1 receptor occupancy of orally administered antihistamines, bepotastine anddiphenhydramine, measured by PET with 11C-doxepin. Br J Clin Pharmacol. 2008 Jun;65(6):811-21.
The physiological and pathophysiological roles of neuronal histamine: an insight from human positronemission tomography studies. Pharmacol Ther. 2007 Jan;113(1):1-15.
Brain histamine H receptor occupancy of orally administered antihistamines measured by positronemission tomography with (11)C-doxepin in a placebo-controlled crossover study design in healthy
subjects: a comparison of olopatadine and ketotifen. Br J Clin Pharmacol. 2006 Jan;61(1):16-26.
Central effects of fexofenadine and cetirizine: measurement of psychomotor performance, subjective
sleepiness, and brain histamine H1-receptor occupancy using 11C-doxepin positron emission tomography.
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