TY - JOUR
T1 - The improved syntheses of 5-substituted 2'-[18F]fluoro-2'-deoxy-arabinofuranosyluracil derivatives ([18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU) using a multistep one-pot strategy
AU - Cai, Hancheng
AU - Li, Zibo
AU - Conti, Peter S.
N1 - Funding Information:
This work was partially supported by research grant DE-SC0002353 from the Department of Energy and the Provost's Biomedical Imaging Science Initiative . We thank Dr. John Fissekis for the help in the design and installation of the reaction module, Joe Cook for [ 18 F]F − ion production and the service support from USC Molecular Imaging Center.
PY - 2011/7
Y1 - 2011/7
N2 - Introduction: We and others have previously reported a four-step radiosynthesis of a series of 2'-deoxy-2'-[18F]fluoro-5-substituted-1-β-d-arabinofuranosyluracil derivatives including [18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU as thymidine derivatives for tumor proliferation and/or reporter gene expression imaging with positron emission tomography (PET). Although the radiosynthesis has been proven to be reproducible and efficient, this complicated multistep reaction is difficult to incorporate into an automated cGMP-compliant radiosynthesis module for routine production. Recently, we have developed a simple and efficient one-pot method for routine production of [18F]FMAU. In this study, we studied the feasibility of radiosynthesizing [18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU using this newly developed method. Methods: Similar to the radiosynthesis of [18F]FMAU, 5-substituted 2'-[18F]fluoro-2'-deoxy-arabinofuranosyluracil derivatives ([18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU) were synthesized in one-pot radiosynthesis module in the presence of Friedel-Crafts catalyst TMSOTf and HMDS. Results: This one-pot radiosynthesis method could be used to produce [18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU. The overall radiochemical yields of these tracers varied from 4.1%±0.8% to 10.1%±1.9% (decay-corrected, n=4). The overall reaction time was reduced from 210 min to 150 min from the end of bombardment, and the radiochemical purity was >99%. Conclusions: The improved radiosyntheses of [18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU have been achieved with reasonable yields and high purity using a multistep one-pot method. The synthetic time has been reduced, and the reaction procedures have been significantly simplified. The success of this approach may make PET tracers [18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU more accessible for preclinical and clinical research.
AB - Introduction: We and others have previously reported a four-step radiosynthesis of a series of 2'-deoxy-2'-[18F]fluoro-5-substituted-1-β-d-arabinofuranosyluracil derivatives including [18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU as thymidine derivatives for tumor proliferation and/or reporter gene expression imaging with positron emission tomography (PET). Although the radiosynthesis has been proven to be reproducible and efficient, this complicated multistep reaction is difficult to incorporate into an automated cGMP-compliant radiosynthesis module for routine production. Recently, we have developed a simple and efficient one-pot method for routine production of [18F]FMAU. In this study, we studied the feasibility of radiosynthesizing [18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU using this newly developed method. Methods: Similar to the radiosynthesis of [18F]FMAU, 5-substituted 2'-[18F]fluoro-2'-deoxy-arabinofuranosyluracil derivatives ([18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU) were synthesized in one-pot radiosynthesis module in the presence of Friedel-Crafts catalyst TMSOTf and HMDS. Results: This one-pot radiosynthesis method could be used to produce [18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU. The overall radiochemical yields of these tracers varied from 4.1%±0.8% to 10.1%±1.9% (decay-corrected, n=4). The overall reaction time was reduced from 210 min to 150 min from the end of bombardment, and the radiochemical purity was >99%. Conclusions: The improved radiosyntheses of [18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU have been achieved with reasonable yields and high purity using a multistep one-pot method. The synthetic time has been reduced, and the reaction procedures have been significantly simplified. The success of this approach may make PET tracers [18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU more accessible for preclinical and clinical research.
KW - PET
KW - Radiosynthesis
KW - [F]-labeling
KW - [F]FAU
KW - [F]FBAU
KW - [F]FCAU
KW - [F]FEAU
KW - [F]FFAU
KW - [F]FIAU
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U2 - 10.1016/j.nucmedbio.2011.01.003
DO - 10.1016/j.nucmedbio.2011.01.003
M3 - Article
C2 - 21718941
AN - SCOPUS:79959684879
SN - 0969-8051
VL - 38
SP - 659
EP - 666
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 5
ER -