title: 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-(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.
authors.affiliation: Vanderbilt University Institute of Imaging Science (VUIIS), Department of Radiology, Nashville, TN,, 37232, USA.
authors.forename: Roman V
authors.initials: RV
authors.lastname: Shchepin
authors.forename: Wellington
authors.initials: W
authors.lastname: Pham
authors.forename: Eduard Y
authors.initials: EY
authors.lastname: Chekmenev
mesh_terms: D000818:Animals; D002247:Carbon Isotopes / Q000737:chemistry; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D005260:Female; D007773:Lactates / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D019344:Lactic Acid / Q000031:analogs & derivatives*; D008325:Mammary Neoplasms, Experimental / Q000175:diagnosis; D051379:Mice; D010766:Phosphorylation; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D002247:Carbon Isotopes; D003287:Contrast Media; D007773:Lactates; D019275:Radiopharmaceuticals; C048984:2-phospholactic acid; D019344:Lactic Acid
keywords: NMR; contrast agent; hyperpolarization; parahydrogen; phospholactate