We aim to develop molecular imaging agents for hyperpolarized 13C magnetic resonance spectroscopy (MRS) that effectively access the intracellular environment of malignant tissue and provide insight into the metabolic profile of tumors. A series of 13C-labeled analogs of tricarboxylic cycle intermediates, which exhibit enhanced cell permeability and are effectively metabolized, will be explored. Through chemical synthesis, systematic modification of carboxylic acid functional groups will yield the corresponding biologically cleavable carboxyl moieties and provide probes with the desired properties. These agents will be assessed to determine ideal candidates and subsequently be employed in hyperpolarized 13C MRS studies of tricarboxylic acid cycle metabolism in cellular and animal models of prostate cancer. New strategies for molecular probe delivery in hyperpolarized 13C MR spectroscopy will offer unique opportunities for targeting specific aspects of tumor metabolism, which will be of broad importance to medicinal chemistry, chemical biology, and medical imaging.
The proposed research focuses on the chemical synthesis and optimization of novel 13C- labeled molecular probes for hyperpolarized metabolic imaging. These probes are designed to enhance membrane transport and efficiently release endogenous substrates in the intracellular environment. Through in vivo studies, we aim to demonstrate that the designed imaging agents effectively evaluate a fundamental characteristic of cancer cells, a metabolic reprogramming for energy production.
|Park, Jae Mo; Wu, Marvin; Datta, Keshav et al. (2017) Hyperpolarized Sodium [1-13C]-Glycerate as a Probe for Assessing Glycolysis In Vivo. J Am Chem Soc 139:6629-6634|