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Title
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Radiosynthesis and in vivo evaluation of -labelled pyrrole-2-carboxamide derivates as novel radioligands for PET imaging of monoamine oxidase A
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Author
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Abstract
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| Introduction Since MAO-A is an enzyme involved in the metabolism of neurotransmitters, fluctuations in MAO-A functionality are associated with psychiatric and neurological disorders as well as with tobacco addiction and behaviour. This study reports the radiolabelling of two [11C]-labelled pyrrole-2-carboxamide derivates, RS 2315 and RS 2360, along with the characterization of their in vivo properties. Methods The radiolabelling of [11C]-RS 2315 and [11C]-RS 2360 was accomplished by alkylation of their amide precursors with [11C]CH3I. Biodistribution, blocking and metabolite studies of both tracers were performed in NMRI mice. Finally, a PET study in Sprague-Dawley rats was performed for [11C]-RS 2360. Results Both tracers were obtained in a radiochemical yield of approximately 30% with radiochemical purity of >98%. Biodistribution studies showed high brain uptake followed by rapid brain clearance for both radiotracers. In the brain, [11C]-RS 2360 was more stable than [11C]-RS 2315. Blocking studies in mice could not demonstrate specificity of [11C]-RS 2315 towards MAO-A or MAO-B. The blocking and imaging study with [11C]-RS 2360 on the other hand indicated specific binding in MAO-A at the earliest time points. Conclusions [11C]-RS 2315 displayed a high nonspecific binding and is therefore not suitable for visualization of MAO-A in vivo. [11C]-RS 2360 on the other hand has potential for mapping MAO-A since specific binding is demonstrated. |
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Language
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English
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Source (journal)
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Nuclear geophysics. - Oxford, 1993, currens
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Publication
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Oxford
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2010
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ISSN
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0969-8086
[print]
1878-6383
[online]
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DOI
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10.1016/J.NUCMEDBIO.2009.09.005
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Volume/pages
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37
:4
(2010)
, p. 459-467
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ISI
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000277701900010
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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