Synthesis of enantiopure 18F-trifluoromethyl cysteine as a structure-mimetic amino acid tracer for glioma imaging

Shaoyu Liu, Hui Ma, Zhanwen Zhang, Liping Lin, Gongjun Yuan, Xiaolan Tang, Dahong Nie, Shende Jiang, Guang Yang, Ganghua Tang
2019 Theranostics  
Although 11 C-labelled sulfur-containing amino acids (SAAs) including L-methyl-[ 11 C]methionine and S-[ 11 C]-methyl-L-cysteine, are attractive tracers for glioma positron emission tomography (PET) imaging, their applications are limited by the short half-life of the radionuclide 11 C (t1/2 = 20.4 min). However, development of 18 F-labelled SAAs ( 18 F, t1/2 = 109.8 min) without significant structural changes or relying on prosthetic groups remains to be a great challenge due to the absence of
more » ... e to the absence of adequate space for chemical modification. Methods: We herein present 18 F-trifluoromethylated D-and L-cysteines which were designed by replacing the methyl group with 18 F-trifluoromethyl group using a structure-based bioisosterism strategy. These two enantiomers were synthesized stereoselectively from serine-derived cyclic sulfamidates via a nucleophilic 18 F-trifluoromethylthiolation reaction followed by a deprotection reaction. Furthermore, we conducted preliminary in vitro and in vivo studies to investigate the feasibility of using 18 F-trifluoromethylated cysteines as PET tracers for glioma imaging. Results: The two-step radiosynthesis provided the desired products in excellent enantiopurity (ee > 99%) with 14% ± 3% of radiochemical yield. In vitro cell study demonstrated that both enantiomers were taken up efficiently by C6 tumor cells and were mainly transported by systems L and ASC. Among them, the D-enantiomer exhibited relatively good stability and high tumor-specific accumulation in the animal studies. Conclusion: Our findings indicate that 18 F-trifluoromethylated D-cysteine, a new SAA tracer, may be a potential candidate for glioma imaging. Taken together, our study represents a first step toward developing 18 F-trifluoromethylated cysteines as structure-mimetic tracers for PET tumor imaging.
doi:10.7150/thno.29405 fatcat:bjhuw6tzujentlnokwz2ijsi4e