UCSF

Background: The acidification of the tumor microenvironment is a result of extensive

metabolic reprogramming in cancer cells and is linked with tumor metastasis. Hyperpolarized

MRI is a method for imaging and quantifying this change in pH, but suffers from rapid signal

loss from spin-lattice (T1) relaxation. We propose using hydrogen/deuterium exchange on

hyperpolarized 13C probes in order to prolong hyperpolarized signal by reducing T1 relaxation.

Methods: H/D exchange was performed on several amino acids and amino acid derivatives

with utility in HP-MRI. Isotopic enrichment was evaluated using 1H NMR. The T1 relaxation

constant was quantified by analyzing the decay of hyperpolarized signal of deuterated vs nondeuterated 13C compounds. Results: H/D exchange was successfully used to enrich compounds

with deuterium with high isotopic enrichment and moderate to high chemical yield. The T1

relaxation constant of all fully analyzed 13C compounds exhibited a significant increase after

deuteration at 3T: T1 of 13C Gly increased from 52.0±3.2 to 65.0±1.2s, 13C Ala from 52.9±2.2

to 66.4±1.7s, 13C Val from 38.1±1.1 to 49.2±0.4s. Conclusion: H/D exchange method

described is a viable technique for inexpensive and direct deuterium labeling. Deuterium

labeling be applied to hyperpolarized 13C MRI probes to prolong HP signal by lengthening T1.