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Evaluation of antihistamine drugs by human [11C]doxepin dynamic PET studies with a parametric image approach

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5 Author(s)
Yun Zhou ; Russell H. Morgan Dept. of Radiol. & Radiol. Sci., Johns Hopkins Univ., Baltimore, MD, USA ; Offord, S. ; Dogan, A.S. ; Crabb, A.H.
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The side effects of sedation induced by antihistamine drugs are considered due to their occupation on cerebral H1 receptor. To evaluate the pharmacological effects of antihistamines on central nervous system quantitatively, PET scans on twelve healthy adults were performed on a GE Advance scanner after intravenous bolus injection of high specific activity [11C]doxepin. Three representative antihistamine drugs used for the treatment of allergy-based diseases,, diphenhydramine, cetirizine, and fexofenadine, were selected in this study for evaluation. Each subject received at least two PET studies in one day, a baseline scan followed by a scan with a single oral therapeutic dose of a tested drug. A linear regression with spatial constraint (LRSC) algorithm derived from a 2-compartmental 3-parameter model was used to estimate the transport rate constant K, and distribution volume (DV). The images of binding potential (BP) were calculated as BP = DV(pixel)/DV(cerebellum)-1. Both PET-toPET intra-subject image registration and spatial normalization using PET template were based on K1 images by using SPM99. The paired T mapping from parametric images were calculated for statistical analysis. Results showed that the model used in this study fits well to the brain tissue [11C]doxepin kinetics measured by PET. The linear operational equations yield a reliable, computationally efficient, and robust LRSC algorithm to generate K1 and DV images. There is no significant effects on K, for the 3 tested drugs. The percent occupancy of diphenhydramine on H1 receptors is 30 to 80% in most cortex regions, and its blocking on H1 receptor in caudate, putamen and thalamus is not significant. Cetirizine is of marginal occupation of H1 receptor in cortex regions in a range of 5 to 20%. Fexofenadine does not have any blockade effects on H1 receptor in brain tissue, and it should be classified as a third generation antihistamine drug.

Published in:

Nuclear Science Symposium Conference Record, 2002 IEEE  (Volume:2 )

Date of Conference:

10-16 Nov. 2002

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