Synthesis of [ ¹⁸ F]Flumazenil ([ ¹⁸ F]FZ)

Multi-patient dose synthesis of [18F]Flumazenil via a copper-mediated 18F-fluorination

“…This compares well with a n.d.c RCY of 35 ± 5% (n = 3) was achieved starting from 23.6 ± 5.8 GBq of [ 18 F]fluoride, the activity of [ 18 F]FMZ in the product vial was between 6.9-9.4 GBq (n.d.c). These RCYs are a significant improvement on the S N Ar method (~ 10%) (vide supra), and comparable to the iodonium method by Moon et al While activity yields have not been widely reported for [ 18 F]FMZ, a detailed report by Schirrmacher et al (2012), reports activity yields of 789 MBq (n = 3) starting from 11-16 GBq of [ 18 F]fluoride. In comparison, this current method produces 7-9 GBq of [ 18 F]FMZ, highlighting the advance using this copper-mediated methods to produce multiple-patients doses from a single production run.…”

“…Despite the advantages of [ 18 F]FMZ over [ 11 C]FMZ, the widespread use of the former has been hampered by low radiochemical yields (RCY), or inaccessibility of requisite precursors. The synthesis of [ 18 F]FMZ from nitromazenil and [ 18 F]fluoride is hindered by the relatively unactivated nature of the arene (Ryzhikov et al 2005;Schirrmacher et al 2012;Kumar et al 2021), and further compounded by the non-trivial separation of the nitromazenil precursor from [ 18 F]FMZ (Massaweh et al 2009;Vaulina et al 2018). An alternative strategy towards [ 18 F]FMZ has featured a diaryliodonium precursor, giving improved radiochemical yields, and was used to support clinical studies.…”

A Molecular Toolbox of Positron Emission Tomography Tracers for General Anesthesia Mechanism Research

“…99 There are several methods to synthesize [ 11 C]28, 99−104 which are now well-established processes performed routinely in many centers worldwide. 105 In the latest report, [ 11 C]28 was successfully prepared by the fully automated iMiDEV microfluidic radio-synthesizer with RCP > 98% and A m = 1912 ± 552 GBq/μmol, 106 which greatly facilitated its clinical research. PET imaging of GABA A receptors with [ 11 C]28 has been used to demonstrate changes in neuronal density, assess the targeting of novel drugs, and study epilepsy 107−112 and cortical damage after stroke or trauma, 113−115 as well as examine patients with Alzheimer's disease 116,117 or toxic leukoencephalopathies, 118 and assist other researches (cerebellar ataxia, 119,120 malignant gliomas, 121 and primary dystonia 122 ).…”

“…The first radioligand used for PET imaging with the GABA A system was 11 C-labeled FMZ ([ 11 C]­FMZ, [ 11 C] 28 ) . There are several methods to synthesize [ 11 C] 28 , − which are now well-established processes performed routinely in many centers worldwide . In the latest report, [ 11 C] 28 was successfully prepared by the fully automated iMiDEV microfluidic radio-synthesizer with RCP > 98% and A m = 1912 ± 552 GBq/μmol, which greatly facilitated its clinical research.…”