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

Kentaro Hatano, Katsuhiko Sekimata, Takashi Yamada, Junichiro Abe, Kengo Ito, Mikako Ogawa, Yasuhiro Magata, Jun Toyohara, Kiichi Ishiwata, Giovanni Biggio, Mariangela Serra, Valentino Laquintana, Nunzio Denora, Andrea Latrofa, Giuseppe Trapani, Gaetano Liso, Hiromi Suzuki, Makoto Sawada, Masahiko Nomura, Hiroshi Toyama

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)325-335
Number of pages11
JournalAnnals of Nuclear Medicine
Volume29
Issue number4
DOIs
Publication statusPublished - 01-05-2015

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Proteins
Oxidopamine
Brain Neoplasms
Intravenous Injections
Radioactivity
Methylation
Carbon
Ischemia
(R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide
CB190 compound
Ligands
Injections
Brain
methyl triflate

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging

Cite this

Hatano, Kentaro ; Sekimata, Katsuhiko ; Yamada, Takashi ; Abe, Junichiro ; Ito, Kengo ; Ogawa, Mikako ; Magata, Yasuhiro ; Toyohara, Jun ; Ishiwata, Kiichi ; Biggio, Giovanni ; Serra, Mariangela ; Laquintana, Valentino ; Denora, Nunzio ; Latrofa, Andrea ; Trapani, Giuseppe ; Liso, Gaetano ; Suzuki, Hiromi ; Sawada, Makoto ; Nomura, Masahiko ; Toyama, Hiroshi. / 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. In: Annals of Nuclear Medicine. 2015 ; Vol. 29, No. 4. pp. 325-335.
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abstract = "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.",
author = "Kentaro Hatano and Katsuhiko Sekimata and Takashi Yamada and Junichiro Abe and Kengo Ito and Mikako Ogawa and Yasuhiro Magata and Jun Toyohara and Kiichi Ishiwata and Giovanni Biggio and Mariangela Serra and Valentino Laquintana and Nunzio Denora and Andrea Latrofa and Giuseppe Trapani and Gaetano Liso and Hiromi Suzuki and Makoto Sawada and Masahiko Nomura and Hiroshi Toyama",
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month = "5",
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doi = "10.1007/s12149-015-0948-8",
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pages = "325--335",
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Hatano, K, Sekimata, K, Yamada, T, Abe, J, Ito, K, Ogawa, M, Magata, Y, Toyohara, J, Ishiwata, K, Biggio, G, Serra, M, Laquintana, V, Denora, N, Latrofa, A, Trapani, G, Liso, G, Suzuki, H, Sawada, M, Nomura, M & Toyama, H 2015, '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', Annals of Nuclear Medicine, vol. 29, no. 4, pp. 325-335. https://doi.org/10.1007/s12149-015-0948-8

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. / Hatano, Kentaro; Sekimata, Katsuhiko; Yamada, Takashi; Abe, Junichiro; Ito, Kengo; Ogawa, Mikako; Magata, Yasuhiro; Toyohara, Jun; Ishiwata, Kiichi; Biggio, Giovanni; Serra, Mariangela; Laquintana, Valentino; Denora, Nunzio; Latrofa, Andrea; Trapani, Giuseppe; Liso, Gaetano; Suzuki, Hiromi; Sawada, Makoto; Nomura, Masahiko; Toyama, Hiroshi.

In: Annals of Nuclear Medicine, Vol. 29, No. 4, 01.05.2015, p. 325-335.

Research output: Contribution to journalArticle

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

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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