title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan.
authors: Pei-Chia
authors: PC
authors: Chan
authors: Chun-Yi
authors: CY
authors: Wu
authors: Wen-Yi
authors: WY
authors: Chang
authors: Wei-Ting
authors: WT
authors: Chang
authors: Mian
authors: M
authors: Alauddin
authors: Ren-Shan
authors: RS
authors: Liu
authors: Wuu-Jyh
authors: WJ
authors: Lin
authors: Fu-Du
authors: FD
authors: Chen
authors: Chuan-Lin
authors: CL
authors: Chen
authors: Hsin-Ell
authors: HE
authors: Wang
mesh_terms: D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D005462:Fluorine Radioisotopes; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D012509:Sarcoma / Q000000981:diagnostic imaging / Q000378:metabolism; D013937:Thymidine Kinase / Q000235:genetics*; D014162:Transfection
chemical_list: D005462:Fluorine Radioisotopes; D003561:Cytarabine; D001086:Arabinofuranosyluracil; C026023:fiacitabine; C043457:fialuridine; C054103:2'-fluoro-5-ethylarabinosyluracil; D013937:Thymidine Kinase