A Practical, Automated Synthesis of meta-[18F]Fluorobenzylguanidine for Clinical Use

Bao Hu, Amy L. Vavere, Kiel D. Neumann, Barry L. Shulkin, Stephen G. DiMagno, Scott E. Snyder

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Many neuroendocrine tumors, such as neuroblastoma (NB), arise from neural crest cells of the sympathetic nervous system. This nerve-like phenotype has been exploited for functional imaging using radioactive probes originally designed for neuronal and adrenal medullary applications. NB imaging with meta-[123I]iodobenzylguanidine ([123I]MIBG) is limited by the emissions of 123I, which lead to poor image resolution and challenges in quantification of its accumulation in tumors. meta-[18F]Fluorobenzylguanidine ([18F]MFBG) is a promising alternative to [123I]MIBG that could change the standard of practice for imaging neuroendocrine tumors, but interest in this PET radiotracer has suffered due to its complex and inefficient radiosynthesis. Here we report a two-step, automated method for the routine production of [18F]MFBG by thermolysis of a diaryliodonium fluoride and subsequent acid deprotection. The synthesis was adapted for use on a commercially available synthesizer for routine production. Full characterization of [18F]MFBG produced by this route demonstrated the tracer's suitability for human use. [18F]MFBG was prepared in almost 3-fold higher yield than previously reported (31% corrected to end of bombardment, n = 9) in a synthesis time of 56 min with >99.9% radiochemical purity. Other than pH adjustment and dilution of the final product, no reformulation was necessary after purification. This method permits the automated production of multidose batches of clinical grade [18F]MFBG. Moreover, if ongoing clinical imaging trials of [18F]MFBG are successful, this methodology is suitable for rapid commercialization and can be easily adapted for use on most commercial automated radiosynthesis equipment.

Original languageEnglish (US)
Pages (from-to)1870-1879
Number of pages10
JournalACS Chemical Neuroscience
Volume6
Issue number11
DOIs
StatePublished - Aug 27 2015

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Keywords

  • [F]MFBG
  • diaryliodonium salts
  • fluorine-18
  • meta-[F]Fluorobenzylguanidine
  • positron emission tomography

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

Cite this

Hu, B., Vavere, A. L., Neumann, K. D., Shulkin, B. L., DiMagno, S. G., & Snyder, S. E. (2015). A Practical, Automated Synthesis of meta-[18F]Fluorobenzylguanidine for Clinical Use. ACS Chemical Neuroscience, 6(11), 1870-1879. https://doi.org/10.1021/acschemneuro.5b00202