Hyperpolarized [2-13C]-fructose: a hemiketal DNP substrate for in vivo metabolic imaging.
Hyperpolarized (13)C 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 T(1) 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 T(1)s (<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 C(2) of fructose is a hemiketal that has a relatively longer relaxation time (approximately 16 s at 37 degrees C) and high solution state polarization (approximately 12%). Hyperpolarized [2-(13)C]-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 T(1) and solution state polarization for ex vivo spectroscopy and in vivo spectroscopic imaging studies.
Department of Radiology and Biomedical Imaging, University of California San Francisco (UCSF), 1700 fourth St., Byers Hall 203, San Francisco, California 94158, USA.
Kayvan R
KR
Keshari
David M
DM
Wilson
Albert P
AP
Chen
Robert
R
Bok
Peder E Z
PE
Larson
Simon
S
Hu
Mark
M
Van Criekinge
Jeffrey M
JM
Macdonald
Daniel B
DB
Vigneron
John
J
Kurhanewicz
D000818:Animals; D002247:Carbon Isotopes; D005632:Fructose / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D011471:Prostatic Neoplasms / Q000378:metabolism; D013057:Spectrum Analysis
D002247:Carbon Isotopes; D005632:Fructose