Assessment of Tumor Redox Status through (S)-4-(3-[18F]fluoropropyl)-L-Glutamic Acid PET Imaging of System xc - Activity.
Cancer Res
; 79(4): 853-863, 2019 02 15.
Article
en En
| MEDLINE
| ID: mdl-30401715
ABSTRACT
The cell's endogenous antioxidant system is vital to maintenance of redox homeostasis. Despite its central role in normal and pathophysiology, no noninvasive tools exist to measure this system in patients. The cystine/glutamate antiporter system xc - maintains the balance between intracellular reactive oxygen species and antioxidant production through the provision of cystine, a key precursor in glutathione biosynthesis. Here, we show that tumor cell retention of a system xc --specific PET radiotracer, (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG), decreases in proportion to levels of oxidative stress following treatment with a range of redox-active compounds. The decrease in [18F]FSPG retention correlated with a depletion of intracellular cystine resulting from increased de novo glutathione biosynthesis, shown through [U-13C6, U-15N2]cystine isotopic tracing. In vivo, treatment with the chemotherapeutic doxorubicin decreased [18F]FSPG tumor uptake in a mouse model of ovarian cancer, coinciding with markers of oxidative stress but preceding tumor shrinkage and decreased glucose utilization. Having already been used in pilot clinical trials, [18F]FSPG PET could be rapidly translated to the clinic as an early redox indicator of tumor response to treatment. SIGNIFICANCE:
[18F]FSPG PET imaging provides a sensitive noninvasive measure of tumor redox status and provides an early marker of tumor response to therapy.See related commentary by Lee et al., p. 701.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Radioisótopos de Flúor
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Cistadenocarcinoma Seroso
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Radiofármacos
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Sistema de Transporte de Aminoácidos y/
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Tomografía de Emisión de Positrones
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Glutamatos
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Res
Año:
2019
Tipo del documento:
Article
País de afiliación:
Reino Unido