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In vivo detection of γ-glutamyl-transferase up-regulation in glioma using hyperpolarized γ-glutamyl-[1-(13)C]glycine

Glutathione (GSH) is often upregulated in cancer, where it serves to mitigate oxidative stress. γ-glutamyl-transferase (GGT) is a key enzyme in GSH homeostasis, and compared to normal brain its expression is elevated in tumors, including in primary glioblastoma. GGT is therefore an attractive imagin...

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Detalles Bibliográficos
Autores principales: Batsios, Georgios, Najac, Chloé, Cao, Peng, Viswanath, Pavithra, Subramani, Elavarasan, Saito, Yutaro, Gillespie, Anne Marie, Yoshihara, Hikari A. I., Larson, Peder, Sando, Shinsuke, Ronen, Sabrina M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148357/
https://www.ncbi.nlm.nih.gov/pubmed/32277103
http://dx.doi.org/10.1038/s41598-020-63160-y
Descripción
Sumario:Glutathione (GSH) is often upregulated in cancer, where it serves to mitigate oxidative stress. γ-glutamyl-transferase (GGT) is a key enzyme in GSH homeostasis, and compared to normal brain its expression is elevated in tumors, including in primary glioblastoma. GGT is therefore an attractive imaging target for detection of glioblastoma. The goal of our study was to assess the value of hyperpolarized (HP) γ-glutamyl-[1-(13)C]glycine for non-invasive imaging of glioblastoma. Nude rats bearing orthotopic U87 glioblastoma and healthy controls were investigated. Imaging was performed by injecting HP γ-glutamyl-[1-(13)C]glycine and acquiring dynamic (13)C data on a preclinical 3T MR scanner. The signal-to-noise (SNR) ratios of γ-glutamyl-[1-(13)C]glycine and its product [1-(13)C]glycine were evaluated. Comparison of control and tumor-bearing rats showed no difference in γ-glutamyl-[1-(13)C]glycine SNR, pointing to similar delivery to tumor and normal brain. In contrast, [1-(13)C]glycine SNR was significantly higher in tumor-bearing rats compared to controls, and in tumor regions compared to normal-appearing brain. Importantly, higher [1-(13)C]glycine was associated with higher GGT expression and higher GSH levels in tumor tissue compared to normal brain. Collectively, this study demonstrates, to our knowledge for the first time, the feasibility of using HP γ-glutamyl-[1-(13)C]glycine to monitor GGT expression in the brain and thus to detect glioblastoma.