TY - JOUR T1 - Synthesis and Evaluation of 2′-Deoxy-2′-<sup>18</sup>F-Fluoro-5-Fluoro-1-β-<span class="sc">d</span>-Arabinofuranosyluracil as a Potential PET Imaging Agent for Suicide Gene Expression JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 2063 LP - 2069 VL - 45 IS - 12 AU - Mian M. Alauddin AU - Antranic Shahinian AU - Ryan Park AU - Michel Tohme AU - John D. Fissekis AU - Peter S. Conti Y1 - 2004/12/01 UR - http://jnm.snmjournals.org/content/45/12/2063.abstract N2 - 2′-Deoxy-2′-18F-fluoro-5-fluoro-1-β-d-arabinofuranosyluracil (18F-FFAU) has been synthesized and evaluated in HT-29 cells as a potential PET agent for herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression. Methods: 2-Deoxy-2-18F-fluoro-1,3,5-tri-O-benzoyl-α-d-arabinofuranose was prepared by the reaction of the respective 2-triflate with tetrabutylammonium 18F-fluoride. The fluorosugar was converted to its 1-bromo derivative and coupled with protected 5-fluorouracil. The crude product was hydrolyzed in base and purified by high-performance liquid chromatography to obtain the 18F-FFAU. In vitro studies were performed in HT-29 cells by incubation at various time points. In vivo studies including biodistribution and microPET were performed in tumor-bearing nude mice. Results: The radiochemical yield was 20%–30% decay corrected with an average of 25% in 4 runs. Radiochemical purity was &gt;99% and average specific activity was 85 GBq/μmol (2,300 mCi/μmol) (end of synthesis). In vitro accumulation of 3H-FFAU in HSV1-tk–expressing cells was ∼180-fold (P &lt; 0.001) higher than that in the wild-type cells between 30 and 120 min. In vivo uptake of 3H-FFAU in HSV1-tk–positive tumors at 2 h was ∼8-fold (P &lt; 0.001) higher than that in the control tumors. Tumor uptake (percentage injected dose per gram of tissue) and the uptake ratio (tk-positive to wild type) of 3H-FFAU in tk-positive cells was higher compared with those of our earlier studies using 2′-14C-deoxy-2′-fluoro-5-methyl-1-β-d-arabinofuranosyluracil (14C-FMAU) and 9-(4-18F-fluoro-3-hydroxymethylbutyl)guanine (18F-FHBG) in the same cell lines. microPET on tumor-bearing nude mice also demonstrated a very high uptake of 18F-FFAU in tk-positive tumors compared with that of the control tumor without significant accumulation in other organs. Conclusion: These results demonstrate that 18F-FFAU has superior biodistribution characteristics and significantly higher in vivo uptake in HSV1-tk–expressing tumor compared with previously studied agents. ER -