Microwave-assisted Radiosynthesis of the Hypoxia Marker 1-α-D-(5- Deoxy-5-[18F]fluoroarabinofuranosyl)-2-nitroimidazole ([18F]FAZA)
Arjun K. Gupta,
Leonard I. Wiebe.
The routine manufacture of most short-lived positron-emitting radiopharmaceuticals (PERs) involves conventional
heating to accelerate the radiolabeling process. Nucleophilic radiofluorination reactions are generally slow at lower
temperatures, and are accompanied by thermal decomposition of both precursor and product at higher temperatures. This
necessitates HPLC purification and results in lower recovered radiochemical yields (rRCYs). [18F]FAZA, a PER for clinical
imaging of focal tissue hypoxia, is routinely manufactured in-house in 3-12% rRCY using a Health Canada approved
conventional heating procedure. The microwave-assisted (MW) radiosynthesis of [18F]FAZA is now reported. Methods:
Manual (MRDS) and automated (ASU) reagent delivery systems coupled to a commercial MW unit were built in-house.
The MW unit controlled power, irradiation time and monitored reaction temperature (Tmax control), while the acetylAZA
tosylate precursor and QMA AccelTM cartridge eluent reagents (K2CO3, K2.2.2) were dispensed by the MRDS or ASU.
The radiofluorination yields (RFYs) and the chemical and radiochemical TLC profiles of the post-labeling reaction mixtures
were compared to those obtained using the conventional heating production method and to those reported for optimized
literature methods. Results: MW RFYs for [18F]FAZA reached >76% (n=3) in 3 min. Post-labeling analysis of the
MW-assisted reaction mixtures demonstrated cleaner UV and radiochemical TLC profiles than those obtained from conventional
heating in routine production runs; the relatively clean MW reactions allowed rapid HPLC isolation of
[18F]FAZA in overall rRCYs of 55±4%. Conclusions: In practical terms, the MW process provided only small gains in reaction
time and RFY, but produced only a few secondary impurities, thereby improving the rRCY in comparison to conventional
heating methods. These findings provide a rationale for adaptation of the MW-assisted method for the routine
production of clinical [18F]FAZA.
Keywords: [18F]FAZA, hypoxia imaging, microwave-assisted radiosynthesis, radiofluorination, RFY, rRCY.
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