Journal of Radioanalytical and Nuclear Chemistry

, Volume 314, Issue 3, pp 1587–1593 | Cite as

Full automatic synthesis of [18F]THK-5351 for tau protein PET imaging in Alzheimer’s disease patients: 1 year experience

  • Sang Ju Lee
  • Seung Jun Oh
  • Eun Hye Cho
  • Da Hye Kim
  • Shozo Furumoto
  • Nobuyuki Okamura
  • Jae Seung Kim
Article
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Abstract

[18F]THK-5351, a new candidate for tau protein imaging, is based on an aryl quinoline structure. We report the full automatic synthesis using disposable cassettes under pH controlled [18F]fluorination. After the trapping of 88.5 ± 21.9 GBq of [18F]fluoride, it was eluted with potassium methansulfonate (KOMs) (pH 7.8)/K222. After drying, 3 mg of the precursor was added to 1 mL DMSO and subjected to [18F]fluorination at 110 °C for 10 min. After hydrolysis, the final product was purified by HPLC. The overall radiochemical yield was 31.9 ± 11.1% (n = 22), satisfying all quality control criteria. It was stable for up to 6 h with high radiochemical purity as 99.8 ± 0.5%.

Keywords

[18F]fluorination THK-5351 Automatic synthesis PET imaging Tau protein positron emission tomography 
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Notes

Acknowledgements

This work was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant Numbers: HI14C1090 & HI14C2768).

References

  1. 1.
    Jack CR Jr, Wiste HJ, Weigand SD, Therneau TM, Knopman DS, Lowe V, Vemuri P, Mielke MM, Roberts RO, Machulda MM, Senjem ML, Gunter JL, Rocca WA, Petersen RC (2017) Age-specific and sex-specific prevalence of cerebral β-amyloidosis, tauopathy, and neurodegeneration in cognitively unimpaired individuals aged 50-95 years: a cross-sectional study. Lancet Neurol 16:435–444CrossRefGoogle Scholar
  2. 2.
    Golla SS, Timmers T, Ossenkoppele R, Groot C, Verfaillie S, Scheltens P, van der Flier WM, Schwarte L, Mintun MA, Devous M, Schuit RC, Windhorst AD, Lammertsma AA, Boellaard R, van Berckel BN, Yaqub M (2017) Quantification of tau load using [18F]AV1451.PET. Mol Imaging Biol (in press)Google Scholar
  3. 3.
    Sepulcre J, Sabuncu MR, Li Q, El Fakhri G, Sperling R, Johnson KA (2017) Tau and amyloid-β proteins distinctively associate to functional network changes in the aging brain. Alzheimers Dement, 1–9Google Scholar
  4. 4.
    Lebouvier T, Pasquier F, Buée L (2017) Update on taupathies. Curr Opin Neurol 30:1–10CrossRefGoogle Scholar
  5. 5.
    Harada R, Ishiki A, Kai H, Sato N, Furukawa K, Furumoto S, Tago T, Tomita N, Watanuki S, Hiraoka K, Ishikawa Y, Funaki Y, Nakamura T, Yoshikawa T, Iwata R, Tashiro M, Sasano H, Kitamoto T, Yanai K, Arai H, Kudo Y, Okamura N (2017) Correlations of 18F-THK5351 PET with post-mortem burden of tau and astrogliosis in Alzheimer’s disease. J Nucl Med (in press)Google Scholar
  6. 6.
    Harada R, Okamura N, Furumoto S, Tago T, Yanai K, Arai H, Kudo Y (2016) Characteristics of tau and its ligands in PET imaging. Biomolecules 6:7–23CrossRefGoogle Scholar
  7. 7.
    Hashimoto H, Kawamura K, Takei M, Igarashi N, Fujishiro T, Shiomi S, Watanabe R, Muto M, Furutsuka K, Ito T, Yamasaki T, Yui J, Nemoto K, Kimura Y, Higuchi M, Zhang MR (2015) Identification of a major radiometabolite of [11C]PBB3. Nucl Med Biol 42:905–910CrossRefGoogle Scholar
  8. 8.
    Wooten DW, Guehl NJ, Verwer EE, Shoup TM, Yokell DL, Zubcevik N, Vasdev N, Zafonte RD, Johnson KA, El Fakhri G, Normandin MD (2017) Pharmacokinetic evaluation of the TauPET radiotracer [18F]T807 ([18F]AV-1451) in human subjects. J Nucl Med 58:484–491CrossRefGoogle Scholar
  9. 9.
    Declercq L, Celen S, Lecina J, Ahamed M, Tousseyn T, Moechars D, Alcazar J, Ariza M, Fierens K, Bottelbergs A, Mariën J, Vandenberghe R, Andres IJ, Van Laere K, Verbruggen A, Bormans G (2016) Comparison of new TauPET-tracer candidates with [18F]T808 and [18F]T807. Mol Imaging 15:1–15CrossRefGoogle Scholar
  10. 10.
    Betthauser T, Lao PJ, Murali D, Barnhart TE, Furumoto S, Okamura N, Stone CK, Johnson SC, Christian BT (2016) In vivo comparison of tau radioligands 18F-THK-5351 and 18F-THK-5317. J Nucl Med (in press)Google Scholar
  11. 11.
    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 (2016) 18F-THK5351: a novel PET radiotracer for imaging neurofibrillary pathology in Alzheimer disease. J Nucl Med 57:208–214CrossRefGoogle Scholar
  12. 12.
    Lee SJ, Oh SJ, Moon DH, Ryu JS (2012) High yielding [18F]fluorination method by fine control of the base. Bull Korean Chem Soc 33:2177–2180CrossRefGoogle Scholar
  13. 13.
    Lee SJ, Hyun JS, Oh SJ, Yu KH, Ryu JS (2013) Development of a new precursor-minimizing base control method and its application for the automated synthesis and SPE purification of [18F]fluoromisonidazole ([18F]FMISO). J Label Comp Radiopharm 56:731–735CrossRefGoogle Scholar
  14. 14.
    Lee SJ, Oh SJ, Moon WY, Choi MS, Kim JS, Chi DY, Moon DH, Ryu JS (2011) New automated synthesis of [18F]FP-CIT with base amount control affording high and stable radiochemical yield: a 1.5-year production report. Nucl Med Biol 38:593–597CrossRefGoogle Scholar
  15. 15.
    Neelamegam R, Yokell DL, Rice PA, Furumoto S, Kudo Y, Okamura N, El Fakhri G (2017) A report of the automated radiosynthesis of the tau positron emission tomography radiopharmaceutical, [18F]-THK-5351. J Label Comp Radiopharm 60:140–146CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2017

Authors and Affiliations

  • Sang Ju Lee
    • 1
  • Seung Jun Oh
    • 1
  • Eun Hye Cho
    • 1
  • Da Hye Kim
    • 1
  • Shozo Furumoto
    • 2
  • Nobuyuki Okamura
    • 2
  • Jae Seung Kim
    • 1
  1. 1.Department of Nuclear Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  2. 2.Department of PharmacologyTohoku University School of MedicineSendaiJapan

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