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

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• 作者：Bao Hu ; Amy L. Va虆vere ; Kiel D. Neumann ; Barry L. Shulkin ; Stephen G. DiMagno ; Scott E. Snyder
• 刊名：ACS Chemical Neuroscience
• 出版年：2015
• 出版时间：November 18, 2015
• 年：2015
• 卷：6
• 期：11
• 页码：1870-1879
• 全文大小：469K
• ISSN：1948-7193

文摘

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鈥檚 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.