Title
Radiosynthesis and in vivo evaluation of <tex>$[^{11}C]$</tex>-labelled pyrrole-2-carboxamide derivates as novel radioligands for PET imaging of monoamine oxidase A Radiosynthesis and in vivo evaluation of <tex>$[^{11}C]$</tex>-labelled pyrrole-2-carboxamide derivates as novel radioligands for PET imaging of monoamine oxidase A
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Subject
Biology
Pharmacology. Therapy
Source (journal)
Nuclear medicine and biology
Volume/pages
37(2010) :4 , p. 459-467
ISSN
0969-8086
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
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.
E-info
https://repository.uantwerpen.be/docman/iruaauth/f1ae87/0e37e159407.pdf