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

TY - JOUR

T1 - Automated synthesis and PET evaluation of both enantiomers of [(18)F]FMISO

AU - Revunov, Evgeny

AU - Jørgensen, Jesper Tranekjær

AU - Jensen, Andreas Ingemann

AU - Hansen, Anders E

AU - Severin, Gregory W

AU - Kjær, Andreas

AU - Zhuravlev, Fedor

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - INTRODUCTION: [(18)F]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 [(18)F]FMISO and compare their PET imaging characteristics.METHODS: The radiosynthesis of enantiopure (R)- and (S)-[(18)F]FMISO was based on Co(salen) (N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminocobalt)-mediated opening of enantiopure epoxides with [(18)F]HF. The uptake and clearance of the individual [(18)F]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 3hours 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)-[(18)F]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/CT scanning revealed a faster initial uptake of the (R)-[(18)F]FMISO enantiomer in tumor and muscle tissues, however the difference became progressively smaller with time. The tumor-to-muscle (T/M) and tumor-to-liver (T/L) ratios remained nearly identical for the (R)- and (S)-forms at all time points. The micro-PET/CT imaging at 1 and 3hours p.i. did not show any significant enantioselective tissue uptake.CONCLUSIONS: Although the (R)-enantiomer of [(18)F]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 [(18)F]FMISO is unlikely to present any practical clinical benefit for PET imaging.

AB - INTRODUCTION: [(18)F]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 [(18)F]FMISO and compare their PET imaging characteristics.METHODS: The radiosynthesis of enantiopure (R)- and (S)-[(18)F]FMISO was based on Co(salen) (N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminocobalt)-mediated opening of enantiopure epoxides with [(18)F]HF. The uptake and clearance of the individual [(18)F]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 3hours 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)-[(18)F]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/CT scanning revealed a faster initial uptake of the (R)-[(18)F]FMISO enantiomer in tumor and muscle tissues, however the difference became progressively smaller with time. The tumor-to-muscle (T/M) and tumor-to-liver (T/L) ratios remained nearly identical for the (R)- and (S)-forms at all time points. The micro-PET/CT imaging at 1 and 3hours p.i. did not show any significant enantioselective tissue uptake.CONCLUSIONS: Although the (R)-enantiomer of [(18)F]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 [(18)F]FMISO is unlikely to present any practical clinical benefit for PET imaging.

U2 - 10.1016/j.nucmedbio.2014.12.010

DO - 10.1016/j.nucmedbio.2014.12.010

M3 - Journal article

C2 - 25595134

SN - 0969-8051

VL - 42

SP - 413

EP - 419

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

IS - 4

ER -