Evaluation of 2'-deoxy-2'-flouro-5-methyl-1-beta-D-arabinofuranosyluracil as a potential gene imaging agent for HSV-tk expression in vivo.
2'-Deoxy-2'-flouro-5-methyl-1-beta-D-arabinofuranosyluracil (FMAU) has been evaluated in HT-29 cells as a potential positron emission tomography (PET) radiotracer for imaging HSV-tk gene expression in vivo. In vitro experiments demonstrate that the accumulation of [14C]-FMAU in HSV-tk-expressing cells is 2.4-fold (p < .02), 4.0-fold (p < .001), and 5.3-fold (p < .001) higher than the wild-type cells at 1, 3, and 5 hr, respectively. In vivo studies revealed that the tumor uptake in HSV-tk-expressing cells was 2.3-fold (p < .001), 3.0-fold (p < .001), and 5.5-fold (p < .001) higher than the control cells at 1, 2, and 5 hr, respectively. FMAU was found to be more sensitive compared to our earlier studies using 9-[(3-18F-fluoro-1-hydroxy-2-propoxy)methyl]-guanine ([18F]-FHPG) and 9-(4-[18F]-fluoro-3-hydroxy-methylbutyl)guanine ([18F]-FHBG) in the same cell lines, although, the specificity was less than FHBG. These results suggest that while FMAU labeled with PET isotopes may be useful for imaging HSV-tk-expressing tumors in vivo, multitracer studies across additional tumor models are necessary in order to identify an optimal PET radiotracer.
Alauddin
Mian M
MM
University of Southern California, USA.
Shahinian
Atranik
A
Gordon
Erlinda M
EM
Conti
Peter S
PS
D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D001692:Biological Transport; D001711:Biotransformation; D002250:Carbon Radioisotopes; D003110:Colonic Neoplasms; D018259:Herpesvirus 1, Human / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011865:Radioisotope Dilution Technique; D011994:Recombinant Proteins / Q000378:metabolism; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000378:metabolism*
D002250:Carbon Radioisotopes; D007202:Indicators and Reagents; D011994:Recombinant Proteins; D001086:Arabinofuranosyluracil; D013937:Thymidine Kinase; C034935:clevudine