Hyperpolarized [1-(13)C]-Pyruvate Magnetic Resonance Spectroscopic Imaging of Prostate Cancer In Vivo Predicts Efficacy of Targeting the Warburg Effect
Autor: | Jeeva Munasinghe, Murali C. Krishna, Yoichi Takakusagi, James Mitchell, Bradley T. Scroggins, Keita Saito, Masayuki Matsuo, Ayla O. White, Vivian Diaz, Deborah Citrin, Carole Sourbier, Kazutoshi Yamamoto, Kazuhiro Ichikawa |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male Cancer Research Article 03 medical and health sciences Prostate cancer chemistry.chemical_compound Mice 0302 clinical medicine Oxygen Consumption DU145 Lactate dehydrogenase Cell Line Tumor Pyruvic Acid medicine Animals Humans Metabolomics Glycolysis Lactic Acid Carbon-13 Magnetic Resonance Spectroscopy Cell Proliferation L-Lactate Dehydrogenase Chemistry Magnetic resonance spectroscopic imaging Cancer Prostatic Neoplasms medicine.disease Warburg effect Magnetic Resonance Imaging Disease Models Animal 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Metabolome Heterografts Pyruvic acid Biomarkers |
Zdroj: | Clin Cancer Res |
Popis: | Purpose: To evaluate the potential of hyperpolarized [1-13C]-pyruvate magnetic resonance spectroscopic imaging (MRSI) of prostate cancer as a predictive biomarker for targeting the Warburg effect. Experimental Design: Two human prostate cancer cell lines (DU145 and PC3) were grown as xenografts. The conversion of pyruvate to lactate in xenografts was measured with hyperpolarized [1-13C]-pyruvate MRSI after systemic delivery of [1-13C] pyruvic acid. Steady-state metabolomic analysis of xenograft tumors was performed with mass spectrometry and steady-state lactate concentrations were measured with proton (1H) MRS. Perfusion and oxygenation of xenografts were measured with electron paramagnetic resonance (EPR) imaging with OX063. Tumor growth was assessed after lactate dehydrogenase (LDH) inhibition with FX-11 (42 μg/mouse/day for 5 days × 2 weekly cycles). Lactate production, pyruvate uptake, extracellular acidification rates, and oxygen consumption of the prostate cancer cell lines were analyzed in vitro. LDH activity was assessed in tumor homogenates. Results: DU145 tumors demonstrated an enhanced conversion of pyruvate to lactate with hyperpolarized [1-13C]-pyruvate MRSI compared with PC3 and a corresponding greater sensitivity to LDH inhibition. No difference was observed between PC3 and DU145 xenografts in steady-state measures of pyruvate fermentation, oxygenation, or perfusion. The two cell lines exhibited similar sensitivity to FX-11 in vitro. LDH activity correlated to FX-11 sensitivity. Conclusions: Hyperpolarized [1-13C]-pyruvate MRSI of prostate cancer predicts efficacy of targeting the Warburg effect. Clin Cancer Res; 24(13); 3137–48. ©2018 AACR. |
Databáze: | OpenAIRE |
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