1: Nucl Med Biol. 2008 Oct;35(7):793-800.

Labelling and biological evaluation of [(11)C]methoxy-Sch225336: a radioligand
for the cannabinoid-type 2 receptor.

Evens N, Bosier B, Lavey BJ, Kozlowski JA, Vermaelen P, Baudemprez L, Busson R,
Lambert DM, Van Laere K, Verbruggen AM, Bormans GM.

Laboratory for Radiopharmacy, K.U.Leuven, Leuven 3000, Belgium.

INTRODUCTION: The cannabinoid type 2 receptor (CB(2) receptor) is part of the
endocannabinoid system and has been suggested as mediator of a number of central 
and peripheral inflammatory processes. In the present study, we have synthesized 
N-[(1s)-1-[4-[[4-methoxy-2-[(4-[(11)C]methoxyphenyl)sulfonyl)-phenyl]sulfonyl]
phenyl]ethyl]methanesulfonamide ([(11)C]methoxy-Sch225336) and evaluated this new
tracer agent as a potential positron emission tomography radioligand for the in
vivo visualization of CB(2) receptors. METHODS: Sch225336 was demethylated and
the resulting phenol precursor was radiolabelled with a carbon-11 methyl group by
methylation using [(11)C]methyl iodide, followed by purification by
high-performance liquid chromatography. The log P of [(11)C]methoxy-Sch225336 and
its biodistribution in normal mice were determined. Enhancement of brain uptake
by inhibition of blood-brain barrier (BBB) efflux transporters was studied. Mouse
plasma was analysed to quantify the formation of radiometabolites. The affinity
of Sch225336 for the human cannabinoid type 1 and type 2 receptor was determined.
RESULTS: [(11)C]methoxy-Sch225336 was obtained with a decay corrected
radiochemical yield of about 30% and a specific activity of 88.8 GBq/mumol (end
of synthesis). After intravenous injection in mice, the compound is rapidly
cleared from the blood through the hepatobiliary pathway and does not show
particular retention in any of the major organs. Polar metabolites were found in 
mouse plasma. Brain uptake was low despite the favourable log P value of 2.15,
which is partly due to efflux by BBB pumps. CONCLUSION: [(11)C]methoxy-Sch225336 
is a good candidate for in vivo imaging of the CB(2) receptor, although the low
blood-brain barrier penetration limits its potential for central nervous system
imaging.


PMID: 18848664 [PubMed - indexed for MEDLINE]

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