Automated synthesis and PET evaluation of both enantiomers of [F-18]FMISO

作者：Revunov Evgeny; Jorgensen Jesper T; Jensen Andreas Ingemann; Hansen Anders E; Severin Gregory W; Kjaer Andreas^*; Zhuravlev Fedor

来源：Nuclear Medicine and Biology, 2015, 42(4): 413-419.

DOI：10.1016/j.nucmedbio.2014.12.010

• [F-18]FMISO
• Hypoxia
• PET
• [(18) F]HF
• Radiofluorination

Introduction: [F-18]FMISO, the widely used positron emission tomography (PET) hypoxia tracer, is a chiral compound clinically used as a racemic mixture. The purpose of this study was to synthesize the individual (R)- and the (S)-enantiomers of [F-18]FMISO and compare their PET imaging characteristics.
Methods: The radiosynthesis of enantiopure (R)- and (S)-[F-18]FMISO was based on Co (salen) (N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminocobalt)-mediated opening of enantiopure epoxides with [F-18]HF. The uptake and clearance of the individual [F-18]FMISO antipodes were investigated using micro-PET/CT imaging performed on mice bearing FaDu tumors. Image-derived biodistribution was obtained from micro-PET/CT scans performed at 1 and 3 hours post injection (p.i.). In addition, the uptake patterns of each enantiomer were observed using two-hour dynamic micro-PET/CT scans, and the time-activity curves from different organs were compared.
Results: The individual (R)- and (S)[F-18]FMISO enantiomers were synthesized in one step with high enantiomeric excess (ee) > 99% and radiochemical purity > 97% using custom-made automation module. The dynamic micro-PET/CF scanning revealed a faster initial uptake of the (R)-[F-18]FMISO enantiomer in tumor and muscle tissues, however the difference became progressively smaller with time. The tumor-to-muscle (T/M) and tumor-toliver (T/L) ratios remained nearly identical for the (R)- and (S)-forms at all time points. The micro-PET/CT imaging at 1 and 3 hours p.i. did not show any significant enantioselective tissue uptake.
Conclusions: Although the (R)-enantiomer of [F-18]FMISO demonstrated a somewhat faster initial tumor and muscle uptake no significant enantioselective tissue uptake was observed at later time points. The T/M- and T/L- ratios for the (R)- and (S)-forms were the same within the experimental error at all times. Therefore, the use of enantiopure [F-18]FMISO is unlikely to present any practical clinical benefit for PET imaging.

• 出版日期2015-4