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Automated Optimized Synthesis of [18F]FLT Using Non-Basic Phase-Transfer Catalyst with Reduced Precursor Amount.

Olga S Fedorova1, Viktoriya V Orlovskaya1, Raisa N Krasikova1

  • 1N.P. Bechtereva Institute of the Human Brain, Russian Academy of Sciences, 197376 St. Petersburg, Russia.

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Summary

This study presents an efficient synthesis of 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT), a PET tracer for tumor proliferation. The new method uses less precursor, simplifying purification and reducing costs for cancer imaging.

Keywords:
3′-deoxy-3′-[18F]fluorothymidine[18F]FLTautomated synthesisfluorine-18radiofluorinationsolid phase extraction

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Area of Science:

  • Radiochemistry
  • Nuclear Medicine
  • Oncology

Background:

  • 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) is a positron emission tomography (PET) tracer vital for assessing tumor proliferation in various cancers.
  • Current [18F]FLT synthesis involves nucleophilic radiofluorination requiring large precursor amounts (20–40 mg), complicating purification, especially with solid-phase extraction (SPE).
  • High precursor quantities lead to increased by-products, posing challenges for achieving high radiochemical purity.

Purpose of the Study:

  • To develop an efficient and simplified method for synthesizing [18F]FLT.
  • To reduce the amount of expensive precursor used in the synthesis.
  • To optimize the purification process for routine clinical use.

Main Methods:

  • Employed tetrabutyl ammonium tosylate as a non-basic phase-transfer catalyst for [18F]FLT synthesis.
  • Significantly reduced the amount of thymidine precursor used.
  • Developed an SPE purification protocol utilizing two specific cartridges (OASIS HLB 6cc and Sep-Pak Alumina N Plus Light) on a GE TRACERlab FX N Pro module.

Main Results:

  • Achieved a radiochemical yield of 16 ± 2% (decay-corrected) for [18F]FLT.
  • Obtained radiochemical purity greater than 99%.
  • Completed synthesis and purification within 55 minutes, with impurities and residual solvents meeting European Pharmacopoeia standards.

Conclusions:

  • The described method offers an efficient, cost-effective, and simplified approach to [18F]FLT synthesis and purification.
  • Reduced precursor consumption leads to fewer by-products and easier purification.
  • The optimized procedure is suitable for automation and utilizes readily available consumables, making it favorable compared to previous methods.