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Synthesis and preliminary biological evaluation of S-11C-methyl-d-cysteine as a new amino acid PET tracer for cancer imaging

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Abstract

S-11C-methyl-l-cysteine (LMCYS) is an attractive amino acid tracer for clinical tumor positron emission tomography (PET) imaging. d-isomers of some radiolabeled amino acids are potential PET tracers for tumor imaging. In this work, S-11C-methyl-d-cysteine (DMCYS), a d-amino acid isomer of S-11C-methyl-cysteine for tumor imaging was developed and evaluated. DMCYS was prepared by 11C-methylation of the precursor d-cysteine, with an uncorrected radiochemical yield over 50 % from 11CH3I within a total synthesis time from 11CO2 about 12 min. In vitro competitive inhibition studies showed that DMCYS uptake was primarily transported through the Na+-independent system L, and also the Na+-dependent system B0,+ and system ASC, with almost no system A. In vitro incorporation experiments indicated that almost no protein incorporation was found in Hepa 1–6 hepatoma cell lines. Biodistribution studies demonstrated higher uptake of DMCYS in pancreas and liver at 5 min post-injection, relatively lower uptake in brain and muscle, and faster radioactivity clearance from most tissues than those of l-isomer during the entire observation time. In the PET imaging of S180 fibrosarcoma–bearing mice and turpentine-induced inflammatory model mice, 2-18F-fluoro-2-deoxy-d-glucose (FDG) exhibited significantly high accumulation in both tumor and inflammatory lesion with low tumor-to-inflammation ratio of 1.40, and LMCYS showed low tumor-to-inflammation ratio of 1.64 at 60 min post-injection. By contrast, DMCYS showed moderate accumulation in tumor and very low uptake in inflammatory lesion, leading to relatively higher tumor-to-inflammation ratio of 2.25 than 11C-methyl-l-methionine (MET) (1.85) at 60 min post-injection. Also, PET images of orthotopic transplanted glioma models demonstrated that low uptake of DMCYS in normal brain tissue and high uptake in brain glioma tissue were observed. The results suggest that DMCYS is a little better than the corresponding l-isomers as a potential PET tumor-detecting agent and is superior to MET and FDG in the differentiation of tumor from inflammation.

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Acknowledgments

This work was supported in part by the Science and Technology Foundation of Guangdong Province (No. 2010B031600054), the National High Technology Research and Development Program of China (863 Program, No. 2008AA02Z430), the National Natural Science Foundation of China (No. 81371584), Science and Technology Planning Project of Guangzhou (2011J5200025), and Doctoral Candidate Innovative Personnel Training Project of Sun Yat-Sen University (2012).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China

    Tingting Huang, Ganghua Tang, Hongliang Wang, Dahong Nie, Xiang Liang, Kongzhen Hu, Chang Yi, Baoguo Yao & Caihua Tang

  2. Department of Applied Chemistry, South China Agricultural University, Guangzhou, 510642, China

    Xiaolan Tang

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  1. Tingting Huang
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  2. Ganghua Tang
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  3. Hongliang Wang
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  5. Xiaolan Tang
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Correspondence to Ganghua Tang.

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Huang, T., Tang, G., Wang, H. et al. Synthesis and preliminary biological evaluation of S-11C-methyl-d-cysteine as a new amino acid PET tracer for cancer imaging. Amino Acids 47, 719–727 (2015). https://doi.org/10.1007/s00726-014-1899-4

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