Dephosphorylation and biodistribution of 1‐13C‐phospholactate in vivo
Abstract
Here, we present a new approach for the delivery of a metabolic contrast agent for in vivo molecular imaging. The use of a phosphate‐protecting group that facilitates parahydrogen‐induced polarization of 1‐13C‐phospholactate potentially enables the in vivo administration of a hydrogenated hyperpolarized adduct. When injected, nonhyperpolarized 1‐13C‐phospholactate is retained in the vasculature during its metabolic conversion to 1‐13C‐lactate by blood phosphatases as demonstrated here using a mucin 1 mouse model of breast cancer and ex vivo high‐resolution 13C NMR. This multisecond process is a suitable mechanism for the delivery of relatively short‐lived 13C and potentially 15N hyperpolarized contrast agents using –OH phosphorylated small molecules, which is demonstrated here for the first time as an example of 1‐13C‐phospholactate. Through this approach, dl‐1‐13C‐lactate is taken up by tissues and organs including the liver, kidneys, brain, heart, and tumors according to a timescale amenable to hyperpolarized magnetic resonance imaging.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 30, 2014
- Source ID
- 10.1002/jlcr.3207
Entities
People
- Eduard Y. Chekmenev
- Roman V. Shchepin
- Wellington Pham
Organizations
- National Institutes of Health
- United States Department of Defense
- Vanderbilt University