Current Radiopharmaceuticals

Sean L. Kitson
Current Radiopharmaceuticals
Almac Sciences
Almac House
20 Seagoe Industrial Estate
Craigavon, BT63 5QD
Northern Ireland


Microwave-assisted Radiosynthesis of the Hypoxia Marker 1-α-D-(5- Deoxy-5-[18F]fluoroarabinofuranosyl)-2-nitroimidazole ([18F]FAZA)

Author(s): Piyush Kumar, Raymond Ortlieb, 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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Article Details

Year: 2014
Page: [49 - 56]
Pages: 8
DOI: 10.2174/1874471007666140711115620