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Synthesis of enantiopure (18)F-trifluoromethyl cysteine as a structure-mimetic amino acid tracer for glioma imaging
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 (t(1/2) = 2...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401404/ https://www.ncbi.nlm.nih.gov/pubmed/30867821 http://dx.doi.org/10.7150/thno.29405 |
Sumario: | 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 (t(1/2) = 20.4 min). However, development of (18)F-labelled SAAs ((18)F, t(1/2) = 109.8 min) without significant structural changes or relying on prosthetic groups remains to be a great challenge due 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. |
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