A novel approach for imaging hypoxia: Tyrosine coupled with 2-nitroimidazole ([18F]FNT])

404 Objectives For hypoxia imaging, radiotracers developed till now possess 2-nitroimidazole (2-NID) due to its capability to follow intracellular metabolism within hypoxic tissues. All tracers ([18F]FMISO, [18F]FAZA)known so far enter the cells by diffusion. As an alternative concept, we linked 2-NID to tyrosine in order to take advantage of the amino acid transporters. Methyl N-[(benzyloxy)carbonyl]-O-[2-{[(4-methylphenyl)sulfonyl]oxy}-3-(2-nitro-1H-imidazol-1-yl)propyl]tyrosine was synthesised for labelling with fluorine-18. Methods [18F]fluoride solution having 3mg K2CO3 and 7mg K222 was dried. Then, 5mg (7.8μmol) of precursor in DMSO (1mL) was added into the activated [18F]KF-K222 complex. Labelling was done at 140°C for 3min. Then, product was eluted with 1mL of 70%TFA from combination of Alumina N Plus and C18 light cartridges. Hydrolysis was done at 120°C. After 20min, the reaction mixture was quenched and purified by HPLC having C18 preparative column using gradient analysis [H2O (A)/MeOH (B)with 2mM HCOONH4,(A:100 to 0%, B: 0 to 100%)] at a flow rate of 5mL/min. Product peak collected at 6.7min was passed through Strata-X cartridge. 500μL of EtOH was used to elute [18F]FNT. Quality control of [18F]FNT (Rt=8.9min) was performed under same HPLC-conditions as for preparative analysis except for flow rate (1mL/min) by using analytical C18 column. Results After the labelling step, RCY was 81±0.9%. For hydrolysis itself, 56±1.5% of RCY was observed. Overall RCY for [18F]FNT (radiochemical purity>98%) was 40% (decay corrected; 90min) at EOS. Conclusions An efficient radiosynthesis for [18F]FNT (40%, overall RCY) was developed including the working up method. For hypoxia studies,2-NID is the important part within [18F]FNT whereas tyrosine with free amino acid function presumably assures transport into the cells