Radiosynthesis and in vivo evaluation of [11C]-labelled pyrrole-2-carboxamide derivates as novel radioligands for PET imaging of monoamine oxidase A.

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 [(11)C]-labelled pyrrole-2-carboxamide derivates, RS 2315 and RS 2360, along with the characterization of their in vivo properties.

Methods: The radiolabelling of [(11)C]-RS 2315 and [(11)C]-RS 2360 was accomplished by alkylation of their amide precursors with [(11)C]CH(3)I. Biodistribution, blocking and metabolite studies of both tracers were performed in NMRI mice. Finally, a PET study in Sprague-Dawley rats was performed for [(11)C]-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, [(11)C]-RS 2360 was more stable than [(11)C]-RS 2315. Blocking studies in mice could not demonstrate specificity of [(11)C]-RS 2315 towards MAO-A or MAO-B. The blocking and imaging study with [(11)C]-RS 2360 on the other hand indicated specific binding in MAO-A at the earliest time points.

Conclusions: [(11)C]-RS 2315 displayed a high nonspecific binding and is therefore not suitable for visualization of MAO-A in vivo. [(11)C]-RS 2360 on the other hand has potential for mapping MAO-A since specific binding is demonstrated.