Synthesis and in vivo evaluation of [C-11]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-[C-11]methyl-1-phe nyl-1,3,8-triaza-spiro[4,5]decan-4-one ([C-11]methyl-Ro 64-6198), a N-methy lated analog of Ro 64-6198, was synthesized and evaluated as a potential ra diopharmaceutical for investigating brain nociceptin/orphanin FQ receptors (ORL1 receptors) by positron emission tomography. A racemate of methyl-Ro 6 4-6198, Ro 66-7931, showed a high affinity and selectivity for the ORL1 rec eptor in vitro. An in vivo distribution study in mice demonstrated moderate brain uptake, however, only slight difference was observed among brain reg ions. Furthermore, pretreating with nociceptin or Ro 66-7931 did not affect the accumulation. Therefore, despite its high affinity, [C-11]methyl-Ro 64 -6198 does not appear to be a suitable tracer for in vivo ORL1 receptor ima ging studies. (C) 2001 Elsevier Science Inc. All rights reserved.