View More View Less
  • 1 Institute of Clinical Physiology, CNR, Via Moruzzi 1, 56124, Pisa, Italy
  • 2 LifeSciences, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights NSW 2234, Australia
Open access

Nucleophilic [18F]-fluorination reactions traditionally include a drying step of the labeling agent in order to achieve a successful substitution. This passage extends the time and complexity required for the whole radiotracer production, with increased hardware and detrimental effects on the radioactive recovery of such a short-lived (t½=109 min) isotope. Because the performance of radiofluorination reactions conducted under microfluidic flow conditions have been demonstrated to be more effective in terms of reaction time and yields, we have tested the tolerance to water present in this specific reaction condition, in view of eliminating the drying step in the process. To this purpose, we tested different substrates selected from typical radiofluorination intermediates. Our results show that water could be tolerated in a microfluidic environment; in particular, we observed a slight decrease in the labeling of aromatic precursors and a significant increase for iodonium salts, whereas the radiochemical yields of the other compounds studied were virtually unchanged. These findings may open the way to the possibility of simpler and faster processes for the production of new 18F-fluorinated positron emission tomography tracers.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Lapi, S. E.; Welch, M. J. Nucl. Med. Biol. 2012, 39, 601608.

  • 2. Cai, L.; Lu, S.; Pike, V. Eur. J. Org. Chem. 2008, 6, 28532873.

  • 3. Kim, H. W.; Jeong, J. M.; Lee, Y. S.; Chi, D. Y.; Chung, K. H.; Lee, D. S.; Chung, J. K.; Lee M. C. Appl. Radiat. Isot. 2004, 61, 12411246.

    • Search Google Scholar
    • Export Citation
  • 4. Kim, D. W.; Jeong, H.-J.; Lim, S. T.; Sohn, M.-H.; Katzenellenbogen, J. A.; Chi, D. Y. J. Org. Chem. 2008, 73, 957962.

  • 5. (a) Aerts, J.; Voccia, S.; Lemaire, C.; Giacomelli, F.; Goblet, D.; Thonon, D.; Plenevaux, A.; Warnock, G.; Luxen, A. Tetra. Lett. 2010, 51, 6466; (b) Lemaire, C. F.; Aerts, J. J.; Voccia, S.; Libert, L. C.; Mercier, F.; Goblet, D.; Plenevaux, A. R.; Luxen, A. J. Angewandte Chemie. 2010, 49, 31613164; (c) Voccia, S.; Aerts, J.; Lemaire, C.; Luxen, A.; Morelle, J.-L.; Philippart, G. WO 2008/128306, 2008.

    • Search Google Scholar
    • Export Citation
  • 6. (a) Hamacher, K.; Coenen, H. H. Appl. Radiat. Isot. 2006, 64, 989994; (b) Saiki, H.; Iwata, R.; Nakanishi, H.; Wong, R.; Ishikawa, Y.; Furumoto, S.; Yamahara, R.; Sakamoto, K.; Ozeki, E. Appl. Radiat. Isot. 2010, 68, 17031708; (c) Wong, R.; Iwata, R.; Saiki, H.; Furumoto, S.; Ishikawa, Y.; Ozeki, E. Appl Radiat Isot, 2012, 70, 193199.

    • Search Google Scholar
    • Export Citation
  • 7. (a) Telu, S.; Chun, J.; Simeon, H. F. G.; Lu, S.; Pike, V. W. Org. Biomol. Chem. 2011, 9, 66296638; (b) Neal, T. R.; Apana, S.; Berridge, M. S. J. Labelled Compd. Radiopharm. 2005, 48, 557568; (c) Arima, V.; Pascali, G.; Lade, O.; Kretschmer, H. R.; Bernsdorf, I.; Hammond, V.; Watts, P.; De Leonardis, F.; Tarn, M. D.; Pamme, N. Lab. Chip. 2013, 13, 23282336; (d) Lang, L.; Eckelman, W. C. Appl. Radiat. Isot. 1994, 45, 11551163.

    • Search Google Scholar
    • Export Citation
  • 8. (a) Pascali, G.; Pitzianti, S.; Del Carlo, S.; Saccomanni, G.; Manera, M.; Macchia, M.; Salvadori, P. A. J. Labelled Compd. Radiopharm. 2011, S502; (b) Pascali, G.; Del Carlo, S.; Saccomanni, G.; Manera, C.; Macchia, M.; Salvadori, P. J. Nucl. Med. Meeting Abstracts 2012, 53, 578.

    • Search Google Scholar
    • Export Citation
  • 9. Watts, P.; Pascali, G.; Salvadori, P. A. J. Flow. Chem. 2012, 2, 3742.

  • 10. Pascali, G.; Kiesewetter, D. O.; Salvadori, P. A.; Eckelman, W. C. J. Labelled Compd. Radiopharm. 2004, 47, 373383.

  • 11. Pascali, G.; Mazzone, G.; Saccomanni, G.; Manera, C.; Salvadori, P. A. Nucl. Med. Biol. 2010, 37, 547555.

  • 12. (a) Dahl, K.; Schou, M.; Halldin, C. J. Labelled Compd. Radiopharm. 2012, 55, 455459; (b) Ungersboeck, J.; Philippe, C.; Mien, L. K.; Haeusler, D.; Shanab, K.; Lanzenberger, R.; Spreitzer, H.; Keppler, B. K.; Dudczak, R.; Kletter, K.; Mitterhauser, M.; Wadsak, W. Nucl. Med. Biol. 2011, 38, 427434.

    • Search Google Scholar
    • Export Citation
  • 13. Pearson, R.G. J. Am. Chem. Soc. 1963, 85, 35333539.

  • 14. Yusubov, M. S.; Svitich, D. Y.; Larkina, M. S.; Zhdankin, V. V. ARKIVOC. 2013, 364395.

  • 15. Chun, J.-H.; Pike, V. W. Eur. J. Org. Chem. 2012, 24, 45414547.

  • 16. Matesic, L.; Wyatt, N. A.; Fraser, B. H.; Roberts, M. P.; Pham, T. Q.; Greguric, I. J. Org. Chem. 2013, 78, 1126211270.