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The present study was performed to determine the safety, distribution, radiation dosimetry, and initial brain imaging of 11C-ITMM in healthy human subjects. Methods: The multiorgan biodistribution and radiation dosimetry of 11C-ITMM were assessed in 3 healthy human subjects, who underwent 2-h whole-body PET scans. Radiation dosimetry was estimated from the normalized number of disintegrations of source organs using the OLINDA/EXM program. Five healthy human subjects underwent 90-min dynamic 11C-ITMM scans of brain regions with arterial blood sampling. For anatomic coregistration, T1-weighted MR imaging was performed. Metabolites in plasma and urine samples were analyzed by high-performance liquid chromatography. 11C-ITMM uptake was assessed quantitatively using a 2-tissue-compartment model. Results: There were no serious adverse events in any of the subjects throughout the study period. 11C-ITMM PET demonstrated high uptake in the urinary bladder and gallbladder, indicating both urinary and fecal excretion of radioactivity. The absorbed dose (muGy/MBq) was highest in the urinary bladder wall (13.2+/-3.5), small intestine (9.8+/-1.7), and liver (9.1+/-2.0). The estimated effective dose for 11C-ITMM was 4.6+/-0.3muSv/MBq. 11C-ITMM showed a gradual increase of radioactivity in the cerebellar cortex. The total distribution volume in the brain regions ranged from 2.61+/-0.30 (cerebellar cortex) to 0.52+/-0.17 (pons), and the rank order of the corresponding total distribution volume of 11C-ITMM was cerebellar cortex \u003e thalamus \u003e frontal cortex \u003e striatum \u0026#8776; pons, which was consistent with the known distribution of mGluR1 in the primate brain. The rate of 11C-ITMM metabolism in plasma was moderate: at 60 min after injection, 62.2%+/-8.2% of the radioactivity in plasma was intact parent compound. Conclusion: The initial findings of the present study indicated that 11C-ITMM PET is feasible for imaging of mGluR1 in the brain. 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lnitial Human PET Studies of Metabotropic Glutamate Receptor Type 1 Ligand 11C-lTMM
https://repo.qst.go.jp/records/46586
https://repo.qst.go.jp/records/465861987692c-bf4b-4e05-ac25-219a0841762b
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2013-08-23 | |||||
タイトル | ||||||
タイトル | lnitial Human PET Studies of Metabotropic Glutamate Receptor Type 1 Ligand 11C-lTMM | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Toyohara, Jun
× Toyohara, Jun× Sakata, Muneyuki× Oda, Keiichi× Ishii, Kenji× Ito, Kimiteru× Hiura, Mikio× Fujinaga, Masayuki× Yamasaki, Tomoteru× Zhang, Ming-Rong× Ishiwata, Kiichi× 藤永 雅之× 山崎 友照× 張 明栄 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-11C-methoxy-N-methylbenzamide (11C-ITMM) is a potential radioligand for mapping metabotropic glutamate receptor type 1 (mGluR1) in the brain by PET. The present study was performed to determine the safety, distribution, radiation dosimetry, and initial brain imaging of 11C-ITMM in healthy human subjects. Methods: The multiorgan biodistribution and radiation dosimetry of 11C-ITMM were assessed in 3 healthy human subjects, who underwent 2-h whole-body PET scans. Radiation dosimetry was estimated from the normalized number of disintegrations of source organs using the OLINDA/EXM program. Five healthy human subjects underwent 90-min dynamic 11C-ITMM scans of brain regions with arterial blood sampling. For anatomic coregistration, T1-weighted MR imaging was performed. Metabolites in plasma and urine samples were analyzed by high-performance liquid chromatography. 11C-ITMM uptake was assessed quantitatively using a 2-tissue-compartment model. Results: There were no serious adverse events in any of the subjects throughout the study period. 11C-ITMM PET demonstrated high uptake in the urinary bladder and gallbladder, indicating both urinary and fecal excretion of radioactivity. The absorbed dose (muGy/MBq) was highest in the urinary bladder wall (13.2+/-3.5), small intestine (9.8+/-1.7), and liver (9.1+/-2.0). The estimated effective dose for 11C-ITMM was 4.6+/-0.3muSv/MBq. 11C-ITMM showed a gradual increase of radioactivity in the cerebellar cortex. The total distribution volume in the brain regions ranged from 2.61+/-0.30 (cerebellar cortex) to 0.52+/-0.17 (pons), and the rank order of the corresponding total distribution volume of 11C-ITMM was cerebellar cortex > thalamus > frontal cortex > striatum ≈ pons, which was consistent with the known distribution of mGluR1 in the primate brain. The rate of 11C-ITMM metabolism in plasma was moderate: at 60 min after injection, 62.2%+/-8.2% of the radioactivity in plasma was intact parent compound. Conclusion: The initial findings of the present study indicated that 11C-ITMM PET is feasible for imaging of mGluR1 in the brain. The low effective dose will permit serial examinations in the same subjects. | |||||
書誌情報 |
Journal of Nuclear Medicine 巻 54, 号 8, p. 1302-1307, 発行日 2013-06 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0161-5505 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.2967/jnumed.113.119891 |