Development of an automated mojule for microscale radiosynthesis of 18F-labeled probes

• Project/Area Number: 16H05383
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: Tohoku University
• Principal Investigator: Iwata Ren 東北大学, サイクロトロン・ラジオアイソトープセンター, 名誉教授 (60143038)
• Co-Investigator(Kenkyū-buntansha): 寺崎 一典 岩手医科大学, 医歯薬総合研究所, 准教授 (60285632) ; 石川 洋一 東北大学, サイクロトロン・ラジオアイソトープセンター, 助手 (60361200)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2016: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: マイクロスケール合成 / ワンポット合成 / フッ素-18 / 18F-標識プローブ / 自動合成 / 標識合成 / PETプローブ / FET / Fallypride / 放射性薬剤 / ワンポット標識合成 / 標識反応

Outline of Final Research Achievements

We have developed a novel and practical method for microscale one-pot radiosynthesis of 18F-labeled probes. Efficient recovery of [18F]fluoride in MeOH from a target water (>90%) and adjustment of the K.222/KHCO3 concentration in a dry MeOH eluate was achieved using disposable ion exchange cartridges (Oasis MAX+MCX). [18F]Fallypride and [18F]FET were successfully synthesized with >80% radiochemical yield in 5-10 μL DMSO after the methods for evaporation of MeOH and MeCN (a solvent for the precursor) and addition of DMSO and precursor solutions had been optimized. These crude products were rapidly purified with an analytical HPLC column. We have also developed an automated module for one-pot microscale radiosynthesis with a microsyringe moving in X-Y axes.

Academic Significance and Societal Importance of the Research Achievements

今やPETによるがん診断や認知症の診断に不可欠となっている18F-標識プローブの合成を、従来の合成法に比べ1/100近くまでスケールダウンして、一滴に相当する5-10μLの反応溶媒量で行う新しいマイクロスケール合成法を世界で初めて開発した。またその自動合成装置を試作した。このマイクロスケール合成法により、使用する試薬量を大幅に減らしながら、これまで以上に効率的でより高品質な18F-標識プローブを再現性良く合成できるようになった。

Research Products

• [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] Site-Specific Labeling of F-18 Proteins Using a Supplemented Cell-Free Protein Synthesis System and O-2-[18F]Fluoroethyl-L-Tyrosine: [18F]FET-HER2 Affibody Molecule (2018)
  • Author(s): Yanai Ai、Harada Ryuichi、Iwata Ren、Yoshikawa Takeo、Ishikawa Yoichi、Furumoto Shozo、Ishida Takanori、Yanai Kazuhiko
  • Journal Title: Molecular Imaging and Biology Volume: - Issue: 3 Pages: 529-537
  • DOI: 10.1007/s11307-018-1266-z
  • Peer Reviewed
• [Journal Article] Neuroimaging-pathological correlations of [(18)F]THK5351 PET in progressive supranuclear palsy (2018)
  • Author(s): Ishiki A, Furukawa K, et al.
  • Journal Title: Acta Neuropathol Commun Volume: 6 Issue: 1 Pages: 53-53
  • DOI: 10.1186/s40478-018-0556-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A comparison of five partial volume correction methods for Tau and Amyloid PET imaging with [(18)F]THK5351 and [(11)C]PIB. (2018)
  • Author(s): Shidahara M, Thomas BA, Okamura N, Ibaraki M, Matsubara K, Oyama S, Ishikawa Y, Watanuki S, Iwata R, Furumoto S, Tashiro M, Yanai K, Gonda K, Watabe H.
  • Journal Title: Ann Nucl Med. Volume: 59 Issue: 7 Pages: 671-674
  • DOI: 10.1007/s12149-017-1185-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Correlations of (18)F-THK5351 PET with Postmortem Burden of Tau and Astrogliosis in Alzheimer Disease. (2018)
  • Author(s): Harada R, Furukawa K, et al.
  • Journal Title: J Nucl Med Volume: 59 Issue: 4 Pages: 671-674
  • DOI: 10.2967/jnumed.117.197426
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Minimization of the amount of Kryptofix 222 - KHCO 3 for applications to microscale 18 F-radiolabeling (2017)
  • Author(s): Iwata Ren、Pascali Claudio、Terasaki Kazunori、Ishikawa Yoichi、Furumoto Shozo、Yanai Kazuhiko
  • Journal Title: Appl. Radiat. Isot. Volume: 125 Pages: 113-118
  • DOI: 10.1016/j.apradiso.2017.04.021
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Continuous-flow synthesis of N-succinimidyl 4-[18F]fluorobenzoate using a single microfluidic chip. (2016)
  • Author(s): Kimura H., Tomatsu K., Saiki H., Arimitsu K., Ono M., Kawashima H., Iwata R., Nakanishi H., Ozeki E., Kuge Y., Saji H.
  • Journal Title: Plos One Volume: 11 Issue: 7 Pages: e0159303-e0159303
  • DOI: 10.1371/journal.pone.0159303
  • NAID: 120005997759
  • Peer Reviewed
• [Journal Article] 18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease (2016)
  • Author(s): Harada R, Okamura N, Furumoto S, Furukawa K, Ishiki A, Tomita N, Tago T, Hiraoka K, Watanuki S, Shidahara M, Miyake M, Ishikawa Y, Matsuda R, Inami A, Yoshikawa T, Funaki Y, Iwata R, Tashiro M, Yanai K, Arai H, Kudo Y
  • Journal Title: J Nucl Med Volume: 57 Issue: 2 Pages: 208-214
  • DOI: 10.2967/jnumed.115.164848
  • Peer Reviewed
• [Journal Article] Radiosynthesis and preliminary biological evaluation of a new 18F-labeled triethylene glycol derivative of triphenylphosphonium. (2016)
  • Author(s): Y., Iwata R., Ishikawa K., Furumoto S.
  • Journal Title: J. Label. Compd. Radiopharm. Volume: 59 Issue: 3 Pages: 117-123
  • DOI: 10.1002/jlcr.3379
  • Peer Reviewed
• [Journal Article] Structure-Activity Relationship of 2-Arylquinolines as PET Imaging Tracers for Tau Pathology in Alzheimer’s Disease (2016)
  • Author(s): Tetsuro Tago, Shozo Furumoto, Nobuyuki Okamura, Ryuichi Harada, Hajime Adachi, Yoichi Ishikawa, Kazuhiko Yanai, Ren Iwata, and Yukitsuka Kudo
  • Journal Title: Journal of Nuclear Medicine Volume: 57(4) Issue: 4 Pages: 608-614
  • DOI: 10.2967/jnumed.115.166652
  • Peer Reviewed
• [Presentation] Microscale radiosynthesis of 18F-labeled compounds (2017)
  • Author(s): Iwata Ren、Pascali Claudio、Terasaki Kazunori、Ishikawa Yoichi、Furumoto Shozo、Yanai Kazuhiko
  • Organizer: 22nd Int. Symp. Radiopharm. Sciences
  • Int'l Joint Research