Synthesis and in vivo evaluation of [11C]methyl-Ro 64-6198 as an ORL1 receptor imaging agent.

(1S,3aS)-8-(2,3,3a,4,5,6-Hexahydro-1H-phenalen-1-yl)-3-N-[11C]methyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one ([11C]methyl-Ro 64-6198), a N-methylated analog of Ro 64-6198, was synthesized and evaluated as a potential radiopharmaceutical for investigating brain nociceptin/orphanin FQ receptors (ORL1 receptors) by positron emission tomography. A racemate of methyl-Ro 64-6198, Ro 66-7931, showed a high affinity and selectivity for the ORL1 receptor in vitro. An in vivo distribution study in mice demonstrated moderate brain uptake, however, only slight difference was observed among brain regions. Furthermore, pretreating with nociceptin or Ro 66-7931 did not affect the accumulation. Therefore, despite its high affinity, [11C]methyl-Ro 64-6198 does not appear to be a suitable tracer for in vivo ORL1 receptor imaging studies.