Synthesis and in vivo evaluation of [11C]SN003 as a PET ligand for CRF1 receptors

Synthesis and evaluation of O-methyl-11C](4-methoxy-2-methylphenyl)1-(1-methoxymethylpropyl)-6-methyl-1H-1,2,3]triazolo4,5-c]pyridin-4-yl]amine or 11C]SN003 (11C]6), as a PET imaging agent for CRF1 receptors, in baboons is described. 4-1-(1-Methoxymethylpropyl)-6-methyl-1H-1,2,3]triazolo4,5-c]pyridin-4-ylamino]-3-methylphenol (5), the precursor molecule for the radiolabeling, was synthesized from 2,4-dichloro-6-methyl-3-nitropyridine in seven steps with 20% overall yield. The total time required for the synthesis of 11C]SN003 is 30 min from EOB using 11C]methyl triflate in the presence of NaOH in acetone. The yield of the synthesis is 22% (EOS) with >99% chemical and radiochemical purities and a specific activity of >2000 Ci/mmol. PET studies in baboon show that 11C]6 penetrates the BBB and accumulates in brain. No detectable specific binding was observed, likely due to the rapid metabolism or low density of CRF1 receptors in primate brain.