Synthesis of 2'-deoxy-2'-[18F]fluoro-5-bromo-1-beta-D-arabinofuranosyluracil ([18F]-FBAU) and 2'-deoxy-2'-[18F]fluoro-5-chloro-1-beta-D-arabinofuranosyl-uracil ([18F]-FCAU), and their biological evaluation as markers for gene expression.
[(18)F]-FBAU and [(18)F]-FCAU have been synthesized and evaluated in vivo as markers for HSV1-tk gene expression. At 2 hours, uptake of [(18)F]-FBAU and [(18)F]-FCAU in HSV1-tk-positive tumors was 7.9-fold and 6.0-fold higher than the control tumors, respectively. Micro-PET images also showed very high uptake in HSV-tk tumors. Compared to [(14)C]-FMAU, total uptake of [(18)F]-FBAU and [(18)F]-FCAU was similar in tk-positive cells, but the uptake ratio (tk+/wild) was higher. [(18)F]-FBAU and [(18)F]-FCAU appear to be potential PET imaging agents for gene expression.
Alauddin
Mian M
MM
Department of Radiology, PET Imaging Science Center, University of Southern California, 2250 Alcazar Street, Suite 135V, Los Angeles, CA 90033, USA. alauddin@usc.edu
Shahinian
Antranic
A
Park
Ryan
R
Tohme
Michel
M
Fissekis
John D
JD
Conti
Peter S
PS
D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001976:Bromouracil / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism*; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009928:Organ Specificity; D011865:Radioisotope Dilution Technique; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013937:Thymidine Kinase / Q000378:metabolism*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods; D014764:Viral Proteins / Q000378:metabolism*
C470854:1-(2-fluoro-2-deoxyarabinofuranosyl)-5-bromouracil; C489864:2'-deoxy-2'-fluoro-5-chloro-1-arabinofuranosyluracil; D014408:Biomarkers, Tumor; D005819:Genetic Markers; D019275:Radiopharmaceuticals; D014764:Viral Proteins; D001086:Arabinofuranosyluracil; D001976:Bromouracil; C099241:thymidine kinase, Canid herpesvirus 1; D013937:Thymidine Kinase; D005472:Fluorouracil