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

ObjectiveHerpes 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′-[18F]fluoro-β-d-arabinofuranosyl)-5-iodocytosine (18F-FIAC) as a new potential positron emission tomography (PET) probe for HSV1-tk gene imaging and compared it with 2’-deoxy-2’-[18F]fluoro-5-iodo-1-β-D-arabinofuranosyluracil (18F-FIAU) and 2’-deoxy-2’-[18F]fluoro-5-ethyl-1-β-D-arabinofuranosyluracil(18F-FEAU) (thymidine analogues) in an NG4TL4-WT/STK sarcoma-bearing mouse model.MethodsA cellular uptake assay, biodistribution study, radioactive metabolites assay and microPET imaging of NG4TL4-WT/STK tumor-bearing mice post administration of 18F-FIAC, 18F-FIAU and 18F-FEAU were conducted to characterize the biological properties of these tracers.ResultsHighly specific uptake of 18F-FIAC, 18F-FIAU and 18F-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, 18F-FIAC showed significant tk(+) tumor specificity (12.6; expressed as the tk(+)-to-tk(−) tumor uptake ratio at 2 h postinjection) comparable with 18F-FIAU (15.8) but lower than 18F-FEAU (48.0). The results of microPET imaging also revealed the highly specific accumulation of these three radioprobes in the NG4TL4-tk(+) tumor.ConclusionOur findings suggested that the cytidine analogue 18F-FIAC is a new potential PET probe for the imaging of HSV1-tk gene expression. 18F-FIAC may be regarded as the prodrug of 18F-FIAU in vivo.