Radiosynthesis and in vivo evaluation of two imidazopyridineacetamides, [¹¹C]CB184 and [¹¹C]CB190, as a PET tracer for 18 kDa translocator protein: direct comparison with [¹¹C](R)-PK11195

Objective: We report synthesis of two carbon-11 labeled imidazopyridines TSPO ligands, [¹¹C]CB184 and [¹¹C]CB190, for PET imaging of inflammatory process along with neurodegeneration, ischemia or brain tumor. Biodistribution of these compounds was compared with that of [¹¹C]CB148 and [¹¹C](R)-PK11195. Methods: Both [¹¹C]CB184 and [¹¹C]CB190 having ¹¹C-methoxyl group on an aromatic ring were readily prepared using [¹¹C]methyl triflate. Biodistribution and metabolism of the compounds were examined with normal mice. An animal PET study using 6-hydroxydopamine treated rats as a model of neurodegeneration was pursued for proper estimation of feasibility of the radioligands to determine neuroinflammation process. Results: [¹¹C]CB184 and [¹¹C]CB190 were obtained via O-methylation of corresponding desmethyl precursor using [¹¹C]methyl triflate in radiochemical yield of 73 % (decay-corrected). In vivo validation as a TSPO radioligand was carried out using normal mice and lesioned rats. In mice, [¹¹C]CB184 showed more uptake and specific binding than [¹¹C]CB190. Metabolism studies showed that 36 % and 25 % of radioactivity in plasma remained unchanged 30 min after intravenous injection of [¹¹C]CB184 and [¹¹C]CB190, respectively. In the PET study using rats, lesioned side of the brain showed significantly higher uptake than contralateral side after i.v. injection of either [¹¹C]CB184 or [¹¹C](R)-PK11195. Indirect Logan plot analysis revealed distribution volume ratio (DVR) between the two sides which might indicate lesion-related elevation of TSPO binding. The DVR was 1.15 ± 0.10 for [¹¹C](R)-PK11195 and was 1.15 ± 0.09 for [¹¹C]CB184. Conclusion: The sensitivity to detect neuroinflammation activity was similar for [¹¹C]CB184 and [¹¹C](R)-PK11195.