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Targeting the Acidic Microenvironment of Prostate Cancer using Chemical Shift-Based, Clinically Translatable Hyperpolarized 13C MRI Biomarkers

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Technical Report,01 Aug 2017,31 Jul 2019

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University of California San Francisco United States

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During the first year of research period, efforts were focused on the synthesis of new classes of hyperpolarized HP 13C agents for probing interstitial pH pHe. Synthesis of13C,15NACES still needs to be optimized but we already reported that deuterium labeling of one the building blocks, 1-13C,2-2H2glycine, led to a significant increase of its relaxation time T1 25 compared to the non-deuterated 13C-labeled glycine. We are convinced that application of this strategy to ACES will also improve its T1, which is a critical property in the development of efficient chemical shift-dependent imaging agents. Optimization of the synthesis of 2-13C,2H10DEMA was successful with high chemical yields and purity. 13C,2Hlabeling is also a key aspect in the potential for DEMA as a candidate for high spatial resolution in vivo pHe mapping. Indeed, DEMA has one of the longest relaxation times measured for HP molecules. We reported the development of DEMA it exhibits a large pH-dependent 13Cchemical shift over the physiological range. We demonstrated that co-polarization with 1-13C,2H9tert-butanol accurately measured pH via 13C NMR and magnetic resonance spectroscopic imaging in phantoms. In vivo experiments enabled us to evaluate DEMA as a clinically translatable HP 13C MRI biomarker.

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  • Medicine and Medical Research
  • Medicine and Medical Research

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