Targeting the Acidic Microenvironment of Prostate Cancer using Chemical Shift-Based, Clinically Translatable Hyperpolarized 13C MRI Biomarkers
Abstract
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 of[13C,15N]ACES still needs to be optimized but we already reported that deuterium labeling of one the building blocks, [1-13C,2-2H2]glycine, 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,2H10]DEMA was successful with high chemical yields and purity. [13C,2H]labeling 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,2H9]tert-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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2019
- Accession Number
- AD1095246
Entities
People
- Céline Taglang
Organizations
- University of California, San Francisco