Optimization of the synthesis and puri cation of 6-[18F]fluoropiperonal, synton for the preparation of complex molecules used as pet tracers

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Abstract

An optimized synthesis method for 6-[18F] uoropiperonal (6-[18F]FP) via nucleophilic sub itution of the nitro group in the precursor molecule (nitropiperonal, 6-NP) with [18F] uoride in the presence of tetrabutylammonium tosylate has been proposed. Using this weakly basic phase transfer catalyst, the amount of initial 6-NP in the reaction was reduced from 4.0 to 0.2 mg with negligible amounts after subsequent treatment of the reaction mixture with a strong base (potassium methoxide). In turn, this made it possible to separate 6-[18F]FP and 6-NP with similar physicochemical properties by a simple and e cient solid-phase extraction technique on disposable cartridges. 6-[18F]FP was obtained with radiochemical purity of 99% and a radiochemical yield of 10%. The content of unreacted 6-NP did not exceed 1 μg/mL, which is comparable to the results of laborious semi-preparative HPLC puri cation.

About the authors

D. D Vaulina

Bechtereva Institute of the Human Brain, Russian Academy of Sciences

V. V Orlovskaya

Bechtereva Institute of the Human Brain, Russian Academy of Sciences

O. S Fedorova

Bechtereva Institute of the Human Brain, Russian Academy of Sciences

O. F Kuznetsova

Bechtereva Institute of the Human Brain, Russian Academy of Sciences

R. N Krasikova

Bechtereva Institute of the Human Brain, Russian Academy of Sciences

Email: raisa@ihb.spb.ru

References

  1. Coenen H.H., Ermert J. // Clin. Transl. Imaging. 2018. Vol. 6. P. 169-193.
  2. Coenen H.H., Elsinga P.H., Iwata R., Kilbourn M.R., Pillai M.R., Rajan M.G., Wagner H.N. Jr, Zaknun J.J. // Nucl. Med. Biol. 2010. Vol. 37. P. 727-740.
  3. van der Born D., Pees A., Poot A.J., Orru R.V.A., Windhorst A.D., Vugts D.J. // Chem. Soc. Rev. 2017. Vol. 46, N 15. P. 4709-4773.
  4. Taïeb D., Imperiale A., Pacak K. // Eur. J. Nucl. Med. Mol. Imaging. 2016. Vol. 43. P. 1187-1189.
  5. Krasikova R.N., Zaitsev V.V., Ametamey S.M., Kuznetsova O.F., Fedorova O.S., Mosevich I.K., Belokon Y.N., Vyskočild Š., Shatik S.V., Nader M., Schubiger P.A. // Nucl. Med. Biol. 2004. Vol. 31. P. 597-603.
  6. Красикова Р.Н., Кузнецова О.Ф., Федорова О.С., Мосевич И.К., Малеев В.И., Белоконь Ю.Н., Савельева Т.Ф., Сагиян А.С., Дадаян С.А., Петросян А.А. // Радиохимия. 2007. Т. 49, № 5. С. 449-454.
  7. Zarrad F., Zlatopolskiy B.D., Urusova E.A., Neumaier B. // J. Label. Compd. Radiopharm. 2015. Vol. 58. S241.
  8. Zarrad F. Ph.D. Dissertation. Köln, Germany: Univ. of Köln, 2017. https://kups.ub.uni-koeln.de/7640/ (accessed Jan. 12, 2022).
  9. Wagner J., Ryazanov S., Leonov A., Levin J., Shi S., Schmidt F., Prix C., Pan-Montojo F., Bertsch U., Mitteregger-Kretzschmar G. et al. // Acta Neuropathol. 2013. Vol. 125. P. 795-813.
  10. Orlovskaya V.V., Fedorova O.S., Viktorov N.B., Vaulina D.D., Krasikova R.N. // Molecules. 2023. Vol. 28. Article 2732.
  11. Krasikova R. // Curr. Org. Chem. 2013. Vol. 17. P. 2097-2107.
  12. Krasikova R.N., Orlovskaya V.V. // Appl. Sci. 2022. Vol. 12, N 1. P. 321.
  13. Wenzel B., Günther R., Brust P., Steinbach J. // J. Chromatogr. A. 2013. Vol. 1311. P. 98-105.
  14. Orlovskaya V., Fedorova O., Nadporojskii M., Krasikova R. // Appl. Radiat. Isot. 2019. Vol. 152. P. 135-139.
  15. Fedorova O.S., Orlovskaya V.V., Nadporojskii M., Krasikova, R.N. // Radiochim. Acta. 2020. Vol. 108. P. 979-988.
  16. Orlovskaya V., Antuganov D., Fedorova O., Timofeev V., Krasikova R. // Appl. Radiat. Isot. 2020. Vol. 163. Article 109195.
  17. Fairway S., Mantzilas D., Horn E., Powell N. // J. Nucl. Med. 2010. Vol. 51 (Suppl. 2). P. 140.
  18. Matsuda H., Ito K., Ishii K., Shimosegawa E., Okazawa H., Mishina M., Mizumura S., Ishii K., Okita K., Shigemoto Y., Kato T., Takenaka A., Kaida H., Hanaoka K., Matsunaga K., Hatazawa J., Ikawa M., Tsujikawa T., Morooka M., Ishibashi K., Kameyama M., Yamao T., Miwa K., Ogawa M., Sato N. // Front. Neurol. 2021. Vol. 11. Article 578753.
  19. Nasirzadeh M., Vaulina D.D., Gomzina N.A. // IX Int. Conf. of Young Scientists on Chemistry "Mendeleev- 2015". Abstract Book. 2015. P. 270-271.
  20. Odano I., Halldin C., Karlsson P., Varrone A., Airaksinen A., Krasikova R.N., Farde L. // Neuroimage. 2009. Vol. 45. P. 891-902.
  21. Liu Y., Zhu L., Plössl K., Choi S.R., Qiao H., Sun X., Li S., Zha Z., Kung H.F. // Nucl. Med. Biol. 2010. Vol. 37. P. 917-925.
  22. Vaulina D., Gomzina N., Nasirzadeh M. // Appl. Radiat. Isot. 2018. Vol. 135. P. 110-114.

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