Synthesis and evaluation of [18F] labeled pyrimidine nucleosides for positron emission tomography imaging of herpes simplex virus 1 thymidine kinase gene expression.
Synthesis of three novel 2'-deoxy-2'-[18F]fluoro-1-beta-D-arabinofuranosyluracil derivatives [18F]FPAU, [18F]FBrVAU, and [18F]FTMAU is reported. The compounds were synthesized by coupling of 1-bromo-2-deoxy-2-fluoro sugars with corresponding silylated uracil derivatives. In vitro cell uptake indicated that all three compounds are taken up selectively in RG2TK+ cells with negligible uptake in RG2 cells. The results indicate that [18F]FBrVAU and [18F]FTMAU have better uptake profiles in comparison to [18F]FPAU and have potential as PET probes for imaging HSV1-tk gene expression.
Pillarsetty
Nagavarakishore
N
Radiochemistry and Cyclotron Core Facility, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.
Cai
Shangde
S
Ageyeva
Lyudmila
L
Finn
Ronald D
RD
Blasberg
Ronald G
RG
D000818:Animals; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D005462:Fluorine Radioisotopes; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000201:enzymology*; D066298:In Vitro Techniques; D015394:Molecular Structure; D049268:Positron-Emission Tomography / Q000379:methods*; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D013237:Stereoisomerism; D013937:Thymidine Kinase / Q000187:drug effects / Q000235:genetics*; D013997:Time Factors
D005462:Fluorine Radioisotopes; D011741:Pyrimidine Nucleosides; D013937:Thymidine Kinase