当前位置： SCI文献检索 > NUCLEAR MEDICINE AND BIOLOGY期刊下所有文献 > [11C]CURB: Evaluation of a novel radiotracer for imaging fatty acid amide hydrolase by positron emission tomography.

[11C]CURB: Evaluation of a novel radiotracer for imaging fatty acid amide hydrolase by positron emission tomography.

Abstract：

INTRODUCTION:Fatty acid amide hydrolase (FAAH) is the enzyme responsible for metabolising the endogenous cannabinoid, anandamide, and thus represents an important target for molecular imaging. To date, no radiotracer has been shown to be useful for imaging of FAAH using either positron emission tomography (PET) or single photon emission computed tomography (SPECT). We here determine the suitability of a novel carbon-11-labeled inhibitor of FAAH via ex vivo biodistribution studies in rat brain in conjunction with pharmacological challenges. METHODS:A potent irreversible inhibitor of FAAH, URB694, radiolabeled with carbon-11 in the carbonyl position ([(11)C]CURB), was administered to male rats via tail-vein injection. Rats were sacrificed at various time points postinjection, and tissue samples were dissected, counted and weighed. Specific binding to FAAH was investigated by pretreatment of animals with URB694 or URB597. For metabolism and mechanism of binding studies, whole brains were excised post-radiotracer injection, homogenised and extracted exhaustively with 80% aq. acetonitrile to determine the time course and fraction of radioactivity that was irreversibly bound to brain parenchyma. RESULTS:Upon intravenous injection into rats, [(11)C]CURB showed high brain uptake [standard uptake value (SUV) of 1.6-2.4 at 5 min] with little washout over time, which is characteristic of irreversible binding. Highest uptake of radioactivity was seen in the cortex, intermediate in the cerebellum and lowest in the hypothalamus, reflecting the reported distribution of FAAH. Brain uptake of radioactivity was decreased in a dose-dependent manner by pretreatment with increasing amounts of URB694, demonstrating that binding was saturable. Pretreatment with the well-characterised FAAH inhibitor, URB597, reduced binding in all brain regions by 70-80%. Homogenised brain extraction experiments demonstrated unequivocally that [(11)C]CURB was irreversibly bound to FAAH. CONCLUSIONS:The title radiotracer demonstrates favourable properties such as good brain uptake, regional heterogeneity and specificity of binding based on ex vivo biodistribution studies in conscious rat brain. [(11)C]CURB represents a highly promising radiotracer for the imaging of FAAH using PET.

journal_name

Nucl Med Biol

journal_title

Nuclear medicine and biology

authors

Wilson AA,Garcia A,Parkes J,Houle S,Tong J,Vasdev N

doi

10.1016/j.nucmedbio.2010.08.001

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

247-53

issue

2

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(10)00408-7

journal_volume

38

pub_type

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