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J Nucl Med. 2008; 49 (Supplement 1):210P
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Neurosciences: Basic Science

Basic Science Posters

Evaluation of [11C]GSK189254 as a novel radioligand for the H3 receptor in human using positron emission tomography (PET)

Sharon Ashworth1, Vincent Cunningham1, Eugennii Rabiner1, Robert Lai2, Tharani Sivananthan2, Christophe Plisson1, Alan Wilson3, Robert Comley1, Antony Gee1 and Marc Laruelle1

1 GlaxoSmithKline Clinical Imaging Centre and Imperial College, London, United Kingdom; 2 NCEDD, GSK, Harlow, United Kingdom; 3 Centre of Addiction and Mental Health (CAMH), Toronto, Ontario, Canada

906

Objectives: The histamine H3 receptor is implicated in the pathophysiology of several CNS disorders. GSK189254 is a highly potent, selective and brain penetrant H3 receptor antagonist. Previous studies in the pig have shown that [11C]GSK189254 uptake in H3 rich regions of the brain can be blocked by the selective H3 antagonist, ciproxifan (1). The aim of this study was to evaluate [11C]GSK189254 in man.

Methods: The regional brain distribution of [11C]GSK189254 was investigated in 14 healthy subjects (35-49y). Each subject was scanned following i.v. administration of ca. 10mCi of [11C]GSK189254 pre and post a single oral dose of GSK189254 (10-100µg).

Results: [11C]GSK189254 readily entered the brain; its regional brain distribution reflected the known distribution of H3 receptors, with high binding in the caudate and putamen, intermediate binding in cortical regions and lower levels in the cerebellum. Pretreatment with oral GSK189254 reduced the uptake of [11C]GSK189254, e.g. following a 50µg dose, VT decreased from 74±27 and 28±4 (n=13) to 16±3 and 12±1 (n=3)(mean±SD) in the caudate and frontal cortex, respectively. Estimates of VND were obtained by graphical analysis (10±1, mean±SD).

Conclusions: [11C]GSK189254 can be used to quantify H3 receptor availability in humans in vivo using PET.





This Article
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Right arrow Email this article to a friend
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Right arrow Alert me to new issues of the journal
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Right arrow Articles by Laruelle, M.
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Right arrow Articles by Ashworth, S.
Right arrow Articles by Laruelle, M.