Development of standardized method for 11C-methionine preparation based on gas-flowlabeling method and solid-phase extraction technique.

• Project/Area Number: 17K10370
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Iwate Medical University
• Principal Investigator: Terasaki Kazunori 岩手医科大学, 医歯薬総合研究所, 准教授 (60285632)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: PET / 自動合成装置 / 脳腫瘍 / 放射性薬剤 / 核薬学 / 自動合成 / 固相抽出

Outline of Final Research Achievements

[11C]Methionine ([11C]MET) is the most commonly used amino acid tracer for PET imaging of brain tumor. A simple and rapid preparation of [11C]MET was achieved with “on column 11C-methylation method” and solid-phase extraction (SPE) method for the formulation. This synthesis method allows a convenient and reliable production of ethanol-free [11C]MET injection with high chemical and radiochemical purities. Further, we have developed a automatic synthesis device for [11C]MET, based on disposable cassettes for the daily routine production.

Academic Significance and Societal Importance of the Research Achievements

現在、多くのPET施設では11Cメチオニン-PETを自由診療として実施している現状がある。一方、先進医療での普及が進まない理由の一因として、合成法および合成装置の抱える課題がボトルネックになっている可能性があげられる。本研究成果として得られた[11C]MET製造法と専用合成装置は、現法に代わる安定で信頼性の高い標準法として、今後の保険診療の適用機器として進展させ、国内外の合成装置メーカーに積極的に働きかけて新たな製造技術を製品開発に結び付けていくことで、PET分野の発展に貢献できるものと期待される。

Research Products

• [Journal Article] Revascularisation surgery improves cognition in adult patients with moyamoya disease. (2020)
  • Author(s): Ando T, Shimada Y, Fujiwara S, Yoshida K, Kobayashi M, Kubo Y, Terasaki K, Ando S, Ogasawara K.
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 91 Issue: 3 Pages: 332-334
  • DOI: 10.1136/jnnp-2019-321069
  • Peer Reviewed
• [Journal Article] Decrease in 18F-Florbetapir Accumulation in the Cerebral Hemisphere With Hypoperfusion and Misery Perfusion Due to Chronic Atherosclerotic Occlusion of the Internal Carotid Artery. (2020)
  • Author(s): Takahashi T, Kobayashi M, Fujiwara S, Kubo Y, Terasaki K, Ogasawara K.
  • Journal Title: Clin Nucl Med Volume: 45 Issue: 2 Pages: e115-e116
  • DOI: 10.1097/rlu.0000000000002774
  • Peer Reviewed
• [Journal Article] Impacts on Histological Features and 11C-Methyl-L-methionine Uptake After “One-Shot” Administration with Bevacizumab Before Surgery in Newly Diagnosed Glioblastoma (2019)
  • Author(s): Beppu Takaaki、Sato Yuichi、Yamada Noriyuki、Terasaki Kazunori、Sasaki Toshiaki、Sugai Tamotsu、Ogasawara Kuniaki
  • Journal Title: Translational Oncology Volume: 12 Issue: 11 Pages: 1480-1487
  • DOI: 10.1016/j.tranon.2019.08.002
  • Peer Reviewed / Open Access
• [Journal Article] Reduced hypoxic tissue and cognitive improvement after revascularization surgery for chronic cerebral ischemia. (2019)
  • Author(s): Shimada Y, Kobayashi M, Yoshida K, Terasaki K, Fujiwara S, Kubo Y, Beppu T, Ogasawara K.
  • Journal Title: Cerebrovasc Dis. Volume: 47 Issue: 1-2 Pages: 57-64
  • DOI: 10.1159/000497244
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Resolution of hypoxic tissue in cerebellar hemispheres after arterial bypass surgery in a patient with symptomatic bilateral vertebral artery occlusion: A 18F-FRP170 PET study. (2019)
  • Author(s): Oikawa K, Kobayashi M, Beppu T, Terasaki K, Ogasawara K.
  • Journal Title: Clin Nucl Med. Volume: 44 Issue: 4 Pages: 295-296
  • DOI: 10.1097/rlu.0000000000002469
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Comparisons between PET with 11C-methyl-L-methionine and arterial spin labeling perfusion imaging in recurrent glioblastomas treated with bevacizumab. (2019)
  • Author(s): Beppu T, Sato Y, Sasaki T, Terasaki K, Yamashita F, Sasaki M, Ogasawara K.
  • Journal Title: Clin Nucl Med. Volume: 44 Issue: 3 Pages: 186-193
  • DOI: 10.1097/rlu.0000000000002417
  • Peer Reviewed / Open Access
• [Journal Article] 18F-FDG and 11C-choline uptake in proliferating tumor cells is dependent on the cell cycle in vitro. (2019)
  • Author(s): Roppongi M, Izumisawa M, Terasaki K, Muraki Y, Shozushima M.
  • Journal Title: Ann Nucl Med. Volume: 33 Issue: 4 Pages: 237-243
  • DOI: 10.1007/s12149-018-01325-6
  • Peer Reviewed
• [Journal Article] Comparison of effects between clopidogrel and cilostazol on cerebral perfusion in nonsurgical adult patients with symptomatically ischemic moyamoya disease: subanalysis of a prospective cohort. (2018)
  • Author(s): Chiba T, Setta K, Shimada Y, Yoshida J, Fujimoto K, Tsutsui S, Yoshida K, Kobayashi M, Kubo Y, Fujiwara S, Terasaki K, Ogasawara K.
  • Journal Title: J Stroke Cerebrovasc Dis. Volume: 27 Issue: 11 Pages: 3373-3379
  • DOI: 10.1016/j.jstrokecerebrovasdis.2018.07.041
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Impact of cerebral blood flow changes due to arterial bypass surgery on cognitive function in adult patients with symptomatic ischemic moyamoya disease. (2018)
  • Author(s): Yanagihara W, Chida K, Kobayashi M, Kubo Y, Yoshida K, Terasaki K, Ogasawara K.
  • Journal Title: J Neurosurg. Volume: 1 Issue: 6 Pages: 1-9
  • DOI: 10.3171/2018.7.jns18149
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Accuracy of brain perfusion single-photon emission computed tomography for detecting misery perfusion in adult patients with symptomatic ischemic moyamoya disease. (2018)
  • Author(s): Setta K, Kojima D, Shimada Y, Yoshida J, Oshida S, Fujimoto K, Tsutsui S, Chiba T, Fujiwara S, Terasaki K, Ogasawara K.
  • Journal Title: Ann Nucl Med. Volume: 32 Issue: 9 Pages: 611-619
  • DOI: 10.1007/s12149-018-1283-7
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Two-year clinical, cerebral hemodynamic, and cognitive outcomes of adult patients undergoing medication alone for symptomatically ischemic moyamoya disease without cerebral misery perfusion: a prospective cohort study. (2018)
  • Author(s): Miyoshi K, Chida K, Kobayashi M, Kubo Y, Yoshida K, Terasaki K, Ogasawara K.
  • Journal Title: Neurosurgery Volume: 30 Issue: 6 Pages: 234-234
  • DOI: 10.1093/neuros/nyy234
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Crossed cerebellar tracer uptake on acute-stage 123I-iomazenil SPECT imaging predicts 3-month functional outcome in patients with non-fatal hypertensive putaminal or thalamic hemorrhage (2018)
  • Author(s): Kojima D, Komoribayashi N, Omama S, Oikawa K, Fujiwara S, Kobayashi M, Kubo Y, Terasaki K, Ogasawara K
  • Journal Title: Clin Nucl Med Volume: 印刷中 Issue: 6 Pages: 396-401
  • DOI: 10.1097/rlu.0000000000002068
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Practical microscale one-pot radiosynthesis of 18F-labeled probes. (2018)
  • Author(s): Iwata R, Pascali C, Terasaki K, Ishikawa Y, Furumoto S, Yanai K.
  • Journal Title: J Label Compd Radiopharm Volume: 17 Issue: 7 Pages: 1-10
  • DOI: 10.1002/jlcr.3618
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Preoperatively reduced cerebrovascular contractile reactivity to hypocapnia by hyperventilation is associated with cerebral hyperperfusion syndrome after arterial bypass surgery for adult patients with cerebral misery perfusion due to ischemic moyamoya disease. (2018)
  • Author(s): Sato S, Kojima D, Shimada Y, Yoshida J, Fujimato K, Fujiwara S, Kobayashi M, Kubo Y, Yoshida K, Terasaki K, Tsutsui S, Miyoshi K, Ogasawara K.
  • Journal Title: J Cereb Blood Flow Metab Volume: 1 Issue: 6 Pages: 1021-1031
  • DOI: 10.1177/0271678x18757621
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Minimization of the amount of Kryptofix 222-KHCO3 for applications to microscale 18F-radiolabeling. (2017)
  • Author(s): Iwata R, Pascali C, Terasaki K, Ishikawa Y, Furumoto S, Yanai K
  • Journal Title: Appl Radiat Isot Volume: 125 Pages: 113-118
  • Peer Reviewed / Open Access
• [Journal Article] Apparent brain temperature imaging with multi-voxel proton magnetic resonance spectroscopy compared with cerebral blood flow and metabolism imaging on positron emission tomography in patients with unilateral chronic major cerebral artery steno-occlusive disease (2017)
  • Author(s): Nanba T, Nishimoto H, Yoshioka Y, Murakami T, Sasaki M, Uwano I, Fujiwara S, Terasaki K, Ogasawara K
  • Journal Title: Neuroradiology Volume: 59 Issue: 9 Pages: 923-935
  • DOI: 10.1007/s00234-017-1890-3
  • Peer Reviewed / Open Access
• [Presentation] A concentration method for efficient microscale one-pot radiosynthesis of [18F]FET and [18F]fallypride. (2019)
  • Author(s): Iwata R, Harada R, Terasaki K, Ishikawa Y, Yanai K.
  • Organizer: 23rd International Symposium on Radiopharmaceutical Sciences
  • Int'l Joint Research
• [Presentation] Feasibility of using apparent brain temperature map on proton magnetic resonance spectroscopy to detect hemodynamic abnormalities in patients with unilateral chronic major cerebral artery steno-occlusive disease. (2019)
  • Author(s): Namba T, Ogasawara K, Yoshioka Y, Sasaki M, Uwano I, Ishigaki D, Kobayashi M, Yoshida K, Fujiwara, Terasaki K.
  • Organizer: 10th Annual Scientific Symposium
  • Int'l Joint Research
• [Presentation] Relation between reduction of hypoxic tissue and cognitive improvement after revascularization surgery in patients with chronic cerebral ischemia. (2019)
  • Author(s): Shimada Y, Kobayashi M, Yoshida K, Terasaki K, Fujiwara S, Kubo Y, Beppu T, Ogasawara K.
  • Organizer: 5th European Stroke Organisation Conference 2019
  • Int'l Joint Research
• [Presentation] Crossed cerebellar tracer uptake on acute-stage 123I-iomazenil SPECT imaging predicts 3-month functional outcome in patients with non-fatal hypertensive putaminal or thalamic hemorrhage. (2019)
  • Author(s): Kojima D, Komoribayashi N, Omama S, Oikawa K, Fujiwara S, Kobayashi M, Kubo Y, Terasaki K, Ogasawara K.
  • Organizer: BRAIN & BRAIN PET 2019
  • Int'l Joint Research
• [Presentation] Feasibility of apparent brain temperature map by 1H-MRS to detect hemodynamic abnormality in patients with unilateral chronic major cerebral artery steno-occlusive disease. (2019)
  • Author(s): Namba T, Ogasawara K, Yoshioka Y, Sasaki M, Uwano I, Ishigaki D, Kobayashi M, Yoshida K, Fujiwara S, Terasaki K.
  • Organizer: BRAIN & BRAIN PET 2019
  • Int'l Joint Research
• [Presentation] 慢性脳虚血に対する血行再建術後の"低酸素環境下生存脳組織"の消失は認知機能改善と関連しているか？ (2019)
  • Author(s): 島田泰良, 小林正和, 吉田研二, 寺崎一典, 藤原俊朗, 久保慶高, 別府高明, 小笠原邦昭
  • Organizer: STROKE 2019
• [Presentation] Preoperative cerebral oxygen extraction fraction imaging generated from 7-tesla magnetic resonance quantitative susceptibility mapping predicts development of cerebral hyperperfusion following carotid endarterectomy. (2018)
  • Author(s): Nomura J, Uwano I, Sasaki M, Kudo K, Yamashita F, Ito K, Fujiwara S, Matsumoto Y, Oikawa K, Chida K, Terasaki K, Kobayashi M, Yoshida K, Ogasawara K.
  • Organizer: the Joint Annual Meeting ISMRM-ESMRMB
  • Int'l Joint Research
• [Presentation] 顎骨浸潤を伴う歯肉癌に対する18F-FDG集積の増大効果 (2018)
  • Author(s): 六本木 基, 小豆島正典、寺崎一典
  • Organizer: 第57回日本核医学会学術総会
• [Presentation] 急性期IMZ-SPECT上のcrossed cerebellar diaschisisは非致死的脳出血の機能転帰を予知する (2018)
  • Author(s): 小島大吾、小守林靖一、大間々真一、及川公樹、藤原俊朗、小林正和、久保慶高、寺崎一典、小笠原邦昭
  • Organizer: 日本脳神経外科学会第77回学術総会
• [Presentation] F-AV-45による脳アミロイド PETを施行したamnestic MCI、AD群の経過の検討 (2018)
  • Author(s): 佐藤光信、米澤久司、工藤雅子、柴田俊秀、小原智子、石塚直樹、高橋純子、寺山靖夫、佐々木敏秋、齋藤義弘、寺崎一典、世良耕一郎
  • Organizer: 第61回日本脳循環代謝学会学術集会
• [Presentation] 急性期IMZ-SPECT上のcrossed cerebellar diaschisisは非致死的脳出血の機能転帰を予知する (2018)
  • Author(s): 小島大吾、小守林靖一、大間々真一、及川公樹、藤原俊朗、小林正和、久保慶高、寺崎一典、小笠原邦昭
  • Organizer: 第61回日本脳循環代謝学会学術集会
• [Presentation] Microscale radiosynthesis of 18F-labeled compounds. (2017)
  • Author(s): Iwata R, Pascali C, Terasaki K, Ishikawa Y, Furumoto S, Yanai
  • Organizer: 22nd International Symposium on Radiopharmaceutical Sciences 2017
  • Int'l Joint Research
• [Presentation] Augmentation effects of lymphocyte activation by antigen-presenting macrophages on 18F-FDG uptake. (2017)
  • Author(s): Roppongi M, Shozushima M, Izumisawa M, Takahashi T, Terasaki K.
  • Organizer: 21st International Congress of Dental and Maxillo-Facial Radiology 2017
  • Int'l Joint Research
• [Presentation] 顎骨浸潤を伴う歯肉癌に対する18F-FDG集積の増大効果 (2017)
  • Author(s): 六本木 基、 小豆島正典、寺崎一典
  • Organizer: 第57回日本核医学会学術総会