A practical, automated synthesis of meta-[(18)F]fluorobenzylguanidine for clinical use

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-[(123)I]iodobenzylguanidine ([(123)I]MIBG) is limited by the emissions of (123)I, which lead to poor image resolution and challenges in quantification of its accumulation in tumors. meta-[(18)F]Fluorobenzylguanidine ([(18)F]MFBG) is a promising alternative to [(123)I]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 [(18)F]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 [(18)F]MFBG produced by this route demonstrated the tracer's suitability for human use. [(18)F]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 [(18)F]MFBG. Moreover, if ongoing clinical imaging trials of [(18)F]MFBG are successful, this methodology is suitable for rapid commercialization and can be easily adapted for use on most commercial automated radiosynthesis equipment.