Synthesis and evaluation of 2'-deoxy-2'-18F-fluoro-5-fluoro-1-beta-D-arabinofuranosyluracil as a potential PET imaging agent for suicide gene expression

Mian M Alauddin, Antranic Shahinian, Ryan Park, Michel Tohme, John D Fissekis, Peter S Conti
Journal of Nuclear Medicine 2004, 45 (12): 2063-9

UNLABELLED: 2'-deoxy-2'-(18)F-fluoro-5-fluoro-1-beta-D-arabinofuranosyluracil ((18)F-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-(18)F-fluoro-1,3,5-tri-O-benzoyl-alpha-D-arabinofuranose was prepared by the reaction of the respective 2-triflate with tetrabutylammonium (18)F-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 (18)F-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 >99% and average specific activity was 85 GBq/micromol (2,300 mCi/micromol) (end of synthesis). In vitro accumulation of (3)H-FFAU in HSV1-tk-expressing cells was approximately 180-fold (P < 0.001) higher than that in the wild-type cells between 30 and 120 min. In vivo uptake of (3)H-FFAU in HSV1-tk-positive tumors at 2 h was approximately 8-fold (P < 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 (3)H-FFAU in tk-positive cells was higher compared with those of our earlier studies using 2'-(14)C-deoxy-2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil ((14)C-FMAU) and 9-(4-(18)F-fluoro-3-hydroxymethylbutyl)guanine ((18)F-FHBG) in the same cell lines. microPET on tumor-bearing nude mice also demonstrated a very high uptake of (18)F-FFAU in tk-positive tumors compared with that of the control tumor without significant accumulation in other organs.

CONCLUSION: These results demonstrate that (18)F-FFAU has superior biodistribution characteristics and significantly higher in vivo uptake in HSV1-tk-expressing tumor compared with previously studied agents.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"