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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-(13)C-phospholactate potentially enables the in vivo administration of a hydrogenated hyperpolarized adduct. When injected, nonhyperpolarized 1-(13)C-phospholactate is retained in the vasculature during its metabolic conversion to 1-(13)C-lactate by blood phosphatases as demonstrated here using a mucin 1 mouse model of breast cancer and ex vivo high-resolution (13)C NMR. This multisecond process is a suitable mechanism for the delivery of relatively short-lived (13)C and potentially (15)N hyperpolarized contrast agents using -OH phosphorylated small molecules, which is demonstrated here for the first time as an example of 1-(13)C-phospholactate. Through this approach, DL-1-(13)C-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.
Copyright © 2014 John Wiley & Sons, Ltd.