Hyperpolarized [2-13C]-Fructose: A Hemiketal DNP Substrate for In Vivo Metabolic Imaging

详细信息    查看全文

• 作者：Kayvan R. Keshari ; David M. Wilson ; Albert P. Chen ; Robert Bok ; Peder E. Z. Larson ; Simon Hu ; Mark Van Criekinge ; Jeffrey M. Macdonald ; Daniel B. Vigneron ; John Kurhanewicz
• 刊名：Journal of the American Chemical Society
• 出版年：2009
• 出版时间：December 9, 2009
• 年：2009
• 卷：131
• 期：48
• 页码：17591-17596
• 全文大小：307K
• 年卷期：v.131,no.48(December 9, 2009)
• ISSN：1520-5126

文摘

Hyperpolarized ¹³C labeled molecular probes have been used to investigate metabolic pathways of interest as well as facilitate in vivo spectroscopic imaging by taking advantage of the dramatic signal enhancement provided by DNP. Due to the limited lifetime of the hyperpolarized nucleus, with signal decay dependent on T₁ relaxation, carboxylate carbons have been the primary targets for development of hyperpolarized metabolic probes. The use of these carbon nuclei makes it difficult to investigate upstream glycolytic processes, which have been related to both cancer metabolism as well as other metabolic abnormalities, such as fatty liver disease and diabetes. Glucose carbons have very short T₁s (<1 s) and therefore cannot be used as an in vivo hyperpolarized metabolic probe of glycolysis. However, the pentose analogue fructose can also enter glycolysis through its phosphorylation by hexokinase and yield complementary information. The C₂ of fructose is a hemiketal that has a relatively longer relaxation time (≈16 s at 37 °C) and high solution state polarization (≈12%). Hyperpolarized [2-¹³C]-fructose was also injected into a transgenic model of prostate cancer (TRAMP) and demonstrated difference in uptake and metabolism in regions of tumor relative to surrounding tissue. Thus, this study demonstrates the first hyperpolarization of a carbohydrate carbon with a sufficient T₁ and solution state polarization for ex vivo spectroscopy and in vivo spectroscopic imaging studies.