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Evaluation of F-18-labeled 5-iodocytidine (18F-FIAC) as a new potential positron emission tomography probe for herpes simplex virus type 1 thymidine kinase imaging.

AbstractOBJECTIVE:
Herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene in combination with radiolabeled nucleoside substrates is the most widely used reporter system. This study characterized 1-(2'-deoxy-2'-[(18)F]fluoro-β-D-arabinofuranosyl)-5-iodocytosine ((18)F-FIAC) as a new potential positron emission tomography (PET) probe for HSV1-tk gene imaging and compared it with 2'-deoxy-2'-[(18)F]fluoro-5-iodo-1-β-D-arabinofuranosyluracil ((18)F-FIAU) and 2'-deoxy-2'-[(18)F]fluoro-5-ethyl-1-β-D-arabinofuranosyluracil((18)F-FEAU) (thymidine analogues) in an NG4TL4-WT/STK sarcoma-bearing mouse model.
METHODS:
A cellular uptake assay, biodistribution study, radioactive metabolites assay and microPET imaging of NG4TL4-WT/STK tumor-bearing mice post administration of (18)F-FIAC, (18)F-FIAU and (18)F-FEAU were conducted to characterize the biological properties of these tracers.
RESULTS:
Highly specific uptake of (18)F-FIAC, (18)F-FIAU and (18)F-FEAU in tk-transfected [tk(+)] cells was observed. The tk(+)-to-tk(-) cellular uptake ratio after a 2-h incubation was 66.6±25.1, 76.3±18.2 and 247.2±37.2, respectively. In biodistribution studies, (18)F-FIAC showed significant tk(+) tumor specificity (12.6; expressed as the tk(+)-to-tk(-) tumor uptake ratio at 2 h postinjection) comparable with (18)F-FIAU (15.8) but lower than (18)F-FEAU (48.0). The results of microPET imaging also revealed the highly specific accumulation of these three radioprobes in the NG4TL4-tk(+) tumor.
CONCLUSION:
Our findings suggested that the cytidine analogue (18)F-FIAC is a new potential PET probe for the imaging of HSV1-tk gene expression. (18)F-FIAC may be regarded as the prodrug of (18)F-FIAU in vivo.
AuthorsPei-Chia Chan, Chun-Yi Wu, Wen-Yi Chang, Wei-Ting Chang, Mian Alauddin, Ren-Shan Liu, Wuu-Jyh Lin, Fu-Du Chen, Chuan-Lin Chen, Hsin-Ell Wang
JournalNuclear medicine and biology (Nucl Med Biol) Vol. 38 Issue 7 Pg. 987-95 (Oct 2011) ISSN: 1872-9614 [Electronic] England
PMID21982570 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Inc. All rights reserved.
Chemical References
  • Fluorine Radioisotopes
  • Cytarabine
  • Arabinofuranosyluracil
  • fiacitabine
  • fialuridine
  • 2'-fluoro-5-ethylarabinosyluracil
  • Thymidine Kinase
Topics
  • Animals
  • Arabinofuranosyluracil (analogs & derivatives, metabolism, pharmacokinetics)
  • Cell Line, Tumor
  • Cytarabine (analogs & derivatives, metabolism, pharmacokinetics)
  • Female
  • Fluorine Radioisotopes
  • Herpesvirus 1, Human (enzymology)
  • Mice
  • Positron-Emission Tomography (methods)
  • Sarcoma (metabolism, radionuclide imaging)
  • Thymidine Kinase (genetics)
  • Transfection

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