Development of a multipurpose microreactor system for preparation of 18F-labeled probes

• Project/Area Number: 25293257
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• 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): FURUMOTO SHOZO 東北大学, サイクロトロン・ラジオアイソトープセンター, 教授 (00375198) ; TAKAHASHI KAZUHIRO 慶応義塾大学, 医学部, 特任准教授 (20370257)
• Co-Investigator(Renkei-kenkyūsha): SAIKI HIDEKAZU 島津製作所, 分析計測事業部, 主任 (70466382)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000); Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2013: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
• Keywords: マイクロリアクター / 標識合成 / 分子イメージング / 自動合成 / 標識プローブ / フッ素-18 / PET / 様式プローブ

Outline of Final Research Achievements

A new microreactor system using electrochemically concentrated [18F]fluoride was developed for preparation of many useful 18F-labeled probes. Novel approaches were evaluated with re-concentration of a reaction solvent in an evaporation flow chip between microfluidic reactions and on-chip 18F-labeling in an electrochemical flow cell where [18F]fluoride was trapped from a flowing water and then released in an aprotic solvent. However, the results showed they were both not promising methods employed for microfluidic reaction. On the other hand, solid phase extraction was successfully adapted to the present system. As a typical demonstration, a hypoxic cell marker [18F]FRP170 was efficiently and rapidly prepared with high qualities as an injection.

Research Products

• [Journal Article] High-uptake areas on positron emission tomography with the hypoxic radiotracer 18F-FRP170 in glioblastomas include regions retaining proliferative activity under hypoxia. (2015)
  • Author(s): Beppu T, Sasaki T, Terasaki K, Saura H, Mtsuura H, Ogasawara K, Sasaki M, Ehara S, Iwata R, Takai Y
  • Journal Title: Ann Nucl Med Volume: 29 Issue: 4 Pages: 336-341
  • DOI: 10.1007/s12149-015-0951-0
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Histamine H receptor occupancy by the new-generation antipsychotics olanzapine and quetiapine: a positron emission tomography study in healthy volunteers (2015)
  • Author(s): Sato, Hirotoshi Ito, Chihiro Hiraoka, Kotaro Tashiro, Manabu Shibuya, Katsuhiko Funaki, Yoshihito Yoshikawa, Takeo Iwata, Ren Matsuoka, Hiroo Yanai, Kazuhiko
  • Journal Title: Psychopharmacology (Berl) Volume: 232 Issue: 19 Pages: 3497-3505
  • DOI: 10.1007/s00213-015-4002-2
  • Peer Reviewed
• [Journal Article] Quantitative kinetic analysis of PET amyloid imaging agents [(11)C]BF227 and [(18)F]FACT in human brain. (2015)
  • Author(s): Shidahara M, Watabe H, Tashiro M, Okamura N, Furumoto S, Watanuki S, Furukawa K, Arakawa Y, Funaki Y, Iwata R, Gonda K, Kudo Y, Arai H, Ishiwata K, Yanai K.
  • Journal Title: Nucl Med Biol. Volume: 42 Issue: 9 Pages: 734-744
  • DOI: 10.1016/j.nucmedbio.2015.05.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Preclinical evaluation of [18F]THK-5015 enantiomers: effects of chirality on its effectiveness as a tau imaging radiotracer. (2015)
  • Author(s): Tago T., Furumoto S., Okamura N., Harada R., Adachi H., Ishikawa Y., Yanai K., Iwata R., Kudo Y.
  • Journal Title: Mol. Imaging Biol. Volume: 未定 Issue: 2 Pages: 258-266
  • DOI: 10.1007/s11307-015-0879-8
  • Peer Reviewed
• [Journal Article] [18F]THK-5117 PET for assessing neurofibrillary pathology in Alzheimer's disease. (2014)
  • Author(s): Harada R, Furukawa K, et al.
  • Journal Title: Eur J Nucl Med Mol Imaging Volume: 42 Issue: 7 Pages: 1052-1061
  • DOI: 10.1007/s00259-015-3035-4
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Standardized uptake value in high uptake area on positron emission tomography with 18F-FRP170 as a hypoxic cell tracer correlates with intratumoral oxygen pressure in glioblastoma (2014)
  • Author(s): Beppu T, Terasaki K, Sasaki T, Fujiwara S, Matsuura H, Ogasawara K, Sera K, Yamada N, Uesugi N, Sugai T, Kudo K, Sasaki M, Ehara S, Iwata R, Takai Y
  • Journal Title: Mol Imaging Biol Volume: 16 Issue: 1 Pages: 127-135
  • DOI: 10.1007/s11307-013-0670-7
  • Peer Reviewed
• [Journal Article] Synthesis and preliminary evaluation of 2-arylhydroxyquinoline derivatives for tau imaging (2014)
  • Author(s): Tetsuro Tago, Shozo Furumoto, Nobuyuki Okamura, Ryuichi Harada, Yoichi Ishikawa, Hiroyuki Arai, Kazuhiko Yanai, Ren Iwata, Yhkitsuka Kudo
  • Journal Title: Journal of Labelled Compounds and Radiopharmaceuticals Volume: 57 Issue: 1 Pages: 18-24
  • DOI: 10.1002/jlcr.3133
  • Peer Reviewed
• [Journal Article] Effects of magnesium deficiency on magnesium uptake activity of rice root, evaluated using 28Mg as a tracer. (2014)
  • Author(s): Tanoi M., Kobayashi N.I., Saito T., Iwata N., Kamada R., Iwata R., Suzuki H., Hirose A., Ohmae Y., Sugita R., Nakanishi T.M.
  • Journal Title: Plant Soil Volume: 384 Pages: 69-77
  • Peer Reviewed
• [Journal Article] Analysis of early phase [11C]BF-227 PET, and its application for anatomical standardization of late-phase images for 3D-SSP analysis. (2014)
  • Author(s): Kaneta T., Okamura N., Arai A., Takanami K., Furukawa K., Tashiro M., Furumoto S., Iwata R., Takahashi S., Arai H., Yanai K., Kudo Y.
  • Journal Title: Jpn. J. Radiol. Volume: 32 Pages: 138-144
  • NAID: 50009030775
  • Peer Reviewed
• [Journal Article] In vitro and vivo characterization of 2-Deoxy-2-〔18F〕Fluoro-D-Mannose as a tumor-imaging agent for positron emission tomography (2013)
  • Author(s): Furumoto S, Shinbo R, Iwata R, Ishikawa Y, Ynai K, Yoshioka T, Fukuda H
  • Journal Title: Journal of Nuclear Medicine Volume: 54 Issue: 8 Pages: 1354-1361
  • DOI: 10.2967/jnumed.112.113571
  • Peer Reviewed
• [Journal Article] Novel 18F-labeled arylquinoline derivatives for non-invasive imaging of tau pathology inAlzheimer’s disease. (2013)
  • Author(s): Okamura N., Furumoto S., Harada R., Tago T., Yoshikawa T., Fodero-Tavoletti M., Mulligan R.S., Villemagne V.L., Akatsu H., Yamamoto T., Arai H., Iwata R., Yanai K., Kudo Y
  • Journal Title: Nucl. Med. Mol. Imag. Volume: 54 Pages: 1420-1427
  • Peer Reviewed
• [Journal Article] A ^<18>F-Labeled BF-227 derivative as a potential radioligand for imaging dense amyloid plaques by positron emission tomography (2013)
  • Author(s): Shozo Furumoto
  • Journal Title: Molecular Imaging and Biology Volume: 15 Issue: 4 Pages: 497-506
  • DOI: 10.1007/s11307-012-0608-5
  • Peer Reviewed
• [Journal Article] Evaluation of the biodistribution and radiation dosimetry of the ^(11)F-labelled amyloid imaging probe [^(18)F]F ACT in humans (2013)
  • Author(s): Shidahara M, Tashiro M, Okamura N, Furumoto S, Furukawa K, Watanuki S, Hiraoka K, Miyake M, Iwata R, Tamura H, Arai H, Kudo Y, Y anai K
  • Journal Title: EJNMMI Res Volume: 3 Issue: 1 Pages: 32-32
  • DOI: 10.1186/2191-219x-3-32
  • Peer Reviewed