TY - JOUR
T1 - Radiosynthesis and in vivo evaluation of two imidazopyridineacetamides, [11C]CB184 and [11C]CB190, as a PET tracer for 18 kDa translocator protein
T2 - direct comparison with [11C](R)-PK11195
AU - Hatano, Kentaro
AU - Sekimata, Katsuhiko
AU - Yamada, Takashi
AU - Abe, Junichiro
AU - Ito, Kengo
AU - Ogawa, Mikako
AU - Magata, Yasuhiro
AU - Toyohara, Jun
AU - Ishiwata, Kiichi
AU - Biggio, Giovanni
AU - Serra, Mariangela
AU - Laquintana, Valentino
AU - Denora, Nunzio
AU - Latrofa, Andrea
AU - Trapani, Giuseppe
AU - Liso, Gaetano
AU - Suzuki, Hiromi
AU - Sawada, Makoto
AU - Nomura, Masahiko
AU - Toyama, Hiroshi
N1 - Funding Information:
The authors would like to thank the members of National Center for Geriatrics and Gerontology for their help. This work was supported by the Research Funding for Longevity Sciences from National Center for Geriatrics and Gerontology, Japan (21-5). All the authors disclose to have no potential conflict of interest.
Publisher Copyright:
© 2015, The Japanese Society of Nuclear Medicine.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
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U2 - 10.1007/s12149-015-0948-8
DO - 10.1007/s12149-015-0948-8
M3 - Article
C2 - 25616581
AN - SCOPUS:84940003915
SN - 0914-7187
VL - 29
SP - 325
EP - 335
JO - Annals of Nuclear Medicine
JF - Annals of Nuclear Medicine
IS - 4
ER -