Abstract
PurposeA rat model was developed to enable direct administration of hyperpolarized 13C‐labeled molecules into a tumor‐supplying artery for magnetic resonance spectroscopy (MRS) studies of tumor metabolism.MethodsRat P22 sarcomas were implanted into the right inguinal fat pad of BDIX rats such that the developing tumors received their principle blood supply directly from the right superior epigastric artery. Hyperpolarized 13C‐molecules were either infused directly to the tumor through the epigastric artery or systemically through the contralateral femoral vein. Spectroscopic data were obtained on a 7 Tesla preclinical scanner.ResultsIntra‐arterial infusion of hyperpolarized 13C‐pyruvate increased the pyruvate tumor signal by a factor of 4.6, compared with intravenous infusion, despite an approximately 7 times smaller total dose to the rat. Hyperpolarized glucose signal was detected at near‐physiological systemic blood concentration. Pyruvate to lactate but not glucose to lactate metabolism was detected in the tumor. Hyperpolarized 13C‐labeled combretastatin A1 diphosphate, a tumor vascular disrupting agent, showed an in vivo signal in the tumor.ConclusionsThe model maximizes tumor substrate/drug delivery and minimizes T1 relaxation signal losses in addition to systemic toxicity. Therefore, it permits metabolic studies of hyperpolarized substrates with relatively short T1 and opens up the possibility for preclinical studies of hyperpolarized drug molecules. Magn Reson Med 78:2116–2126, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Highlights
Hyperpolarized dissolution dynamic nuclear polarization is an established technology for in vivo monitoring of metabolism by magnetic resonance spectroscopy (MRS) and MRI, without the interfering background signals experienced in 1H MRS [1,2]
The hyperpolarized substrate is rapidly administered to experimental animals, and signals are acquired from metabolites within a few multiples of the T1 relaxation time, before the signal decay becomes too significant
The initial change in image intensity was typically first observed at approximately 9 s - similar to that observed for hyperpolarized pyruvate and glucose, as described subsequently
Summary
Hyperpolarized dissolution dynamic nuclear polarization (dDNP) is an established technology for in vivo monitoring of metabolism by magnetic resonance spectroscopy (MRS) and MRI, without the interfering background signals experienced in 1H MRS [1,2]. The hyperpolarized substrate is rapidly administered to experimental animals, and signals are acquired from metabolites within a few multiples of the T1 relaxation time, before the signal decay becomes too significant. The most commonly used hyperpolarized substrate, 13C1pyruvate, has a reported T1 of approximately 50 s for in vitro aqueous solutions, whereas in vivo values, including those for extracted blood, have been estimated in the range of 17 to 30 s [3,4,5].
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