Synthesis and Evaluation of 2′-Deoxy-2′-18F-Fluoro-5-Fluoro-1-β-d-Arabinofuranosyluracil as a Potential PET Imaging Agent for Suicide Gene Expression

Journal of Nuclear Medicine

Ryan Park¹  Antranic Shahinian¹  Mian M. Alauddin¹  Michel Tohme¹  Peter S. Conti¹  John D. Fissekis¹ 

[1] PET Imaging Science Center, Department of Radiology, University of Southern California, Los Angeles, California PET Imaging Science Center, Department of Radiology, University of Southern California, Los Angeles, California PET Imaging Science Center, Department of Radiology, University of Southern California, Los Angeles, California

关键词: 2′-deoxy-2′-¹⁸F-fluoro-5-fluoro-1-β-d-arabinofuranosyluracil;    herpes simplex virus type-1 thymidine kinase;    HT-29 cells;    PET;    gene expression;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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 >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 < 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 < 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.

【 授权许可】

Unknown