TY - JOUR
T1 - Towards hyperpolarized 13C-succinate imaging of brain cancer
AU - Bhattacharya, Pratip
AU - Chekmenev, Eduard Y.
AU - Perman, William H.
AU - Harris, Kent C.
AU - Lin, Alexander P.
AU - Norton, Valerie A.
AU - Tan, Chou T.
AU - Ross, Brian D.
AU - Weitekamp, Daniel P.
N1 - Funding Information:
This work was generously supported by Rudi Schulte Research Institutes (E.Y.C., A.P.L.), James G. Boswell Fellowship (P.B.), Mildred Swanson/American Brain Tumor Association Fellowship (P.B.), American Heart Association Fellowship (P.B.), NARSAD Young Investigator Award (K.C.H.), Beckmann Institute Resource Center Pilot Award (V.A.N., D.P.W.) and performed under research Grant 1R21 CA118509 from National Cancer Institute (P.B.). The polarizer was provided under loan agreement between HMRI and GE Healthcare established by Dr. Klaes Golman, Ms. Marivi Mendizabal and Jonathan Murray. Preliminary advice from Dr. Oskar Axelson and colleagues at Amersham Bioscience, Malmo, Sweden is much appreciated. We thank Dr. Keiko Kanamori (HMRI) for advice and Jan Hövener for technical support. Prof. Brian D. Ross, University of Michigan, Ann Arbor, prepared and supplied 9L tumor bearing rats.
PY - 2007/5
Y1 - 2007/5
N2 - We describe a novel 13C enriched precursor molecule, sodium 1-13C acetylenedicarboxylate, which after hydrogenation by PASADENA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized 13C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized 13C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized 13C sodium succinate, contained significant concentrations of the injected substrate, 13C sodium succinate, together with 13C maleate and succinate metabolites 1-13C-glutamate, 5-13C-glutamate, 1-13C-glutamine and 5-13C-glutamine. The 13C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood-brain barrier. These ex vivo results indicate that hyperpolarized 13C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in 13C MR spectral-spatial images.
AB - We describe a novel 13C enriched precursor molecule, sodium 1-13C acetylenedicarboxylate, which after hydrogenation by PASADENA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized 13C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized 13C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized 13C sodium succinate, contained significant concentrations of the injected substrate, 13C sodium succinate, together with 13C maleate and succinate metabolites 1-13C-glutamate, 5-13C-glutamate, 1-13C-glutamine and 5-13C-glutamine. The 13C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood-brain barrier. These ex vivo results indicate that hyperpolarized 13C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in 13C MR spectral-spatial images.
KW - 9L tumor
KW - Acetylenedicarboxylate
KW - C
KW - Ex vivo spectroscopy
KW - Glutamine
KW - Hyperpolarization
KW - In vivo imaging
KW - PASADENA
KW - Succinate
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U2 - 10.1016/j.jmr.2007.01.017
DO - 10.1016/j.jmr.2007.01.017
M3 - Article
C2 - 17303454
AN - SCOPUS:34247464785
SN - 1090-7807
VL - 186
SP - 150
EP - 155
JO - Journal of Magnetic Resonance
JF - Journal of Magnetic Resonance
IS - 1
ER -