Hyperpolarized [1- 13 C]-Pyruvate Magnetic Resonance Spectroscopic Imaging of Prostate Cancer In Vivo Predicts Efficacy of Targeting the Warburg Effect.

Autor:	Scroggins BT; Radiation Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland., Matsuo M; Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland., White AO; Radiation Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland., Saito K; Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland., Munasinghe JP; National Institute of Neurological Disorder and Stroke, NIH, Bethesda, Maryland., Sourbier C; Urologic Oncology Branch, Center for Cancer Research, NIH, Bethesda, Maryland., Yamamoto K; Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland., Diaz V; National Institute of Neurological Disorder and Stroke, NIH, Bethesda, Maryland., Takakusagi Y; Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Ichikawa K; Department of Pharmacy, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki, Japan., Mitchell JB; Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland., Krishna MC; Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland., Citrin DE; Radiation Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland. citrind@mail.nih.gov.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2018 Jul 01; Vol. 24 (13), pp. 3137-3148. Date of Electronic Publication: 2018 Mar 29.
DOI:	10.1158/1078-0432.CCR-17-1957
Abstrakt:	Purpose: To evaluate the potential of hyperpolarized [1- 13 C]-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- 13 C]-pyruvate MRSI after systemic delivery of [1- 13 C] pyruvic acid. Steady-state metabolomic analysis of xenograft tumors was performed with mass spectrometry and steady-state lactate concentrations were measured with proton ( 1 H) 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- 13 C]-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- 13 C]-pyruvate MRSI of prostate cancer predicts efficacy of targeting the Warburg effect. Clin Cancer Res; 24(13); 3137-48. ©2018 AACR . (©2018 American Association for Cancer Research.)
Databáze:	MEDLINE
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