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Facile Synthesis [5-(13)C-4-(2)H(2)]-L-Glutamine for Hyperpolarized MRS Imaging of Cancer Cell Metabolism.
MedLine Citation:
PMID:  21658976     Owner:  NLM     Status:  Publisher    
RATIONALE AND OBJECTIVES: Recent reports suggest that cancer cells may use glutamine, instead of glucose, as an alternative source of metabolic energy. This suggests that hyperpolarized (13)C glutamine may be useful as a magnetic resonance spectroscopy (MRS) imaging agent for detecting changes in glutamine metabolism in cancerous cells or tissues. MATERIALS AND METHODS: Synthesis of [5-(13)C-4-(2)H(2)]-L-glutamine was accomplished through a seven-step synthetic pathway with a 44% overall yield. The introduction of two stable isotopes was performed by a NaB(2)H(4)-mixed anhydride reduction and K(13)CN-nuclophilic substitution, respectively. The desired [5-(13)C-4-(2)H(2)]-L-glutamine was successfully obtained by a one-pot reaction of deprotection and controlled cyanide hydrolysis. Hyperpolarized [5-(13)C-4-(2)H(2)]-L-glutamine samples were tested in human glioma cells (myc upregulated glia cells, SF188-Bcl-x(L)). MRS signals were obtained with a 9.4 Tesla 89-mm bore nuclear magnetic resonance spectrometer and a direct-detection multi-nuclear probe. RESULTS: The initial degree of polarization for [5-(13)C-4-(2)H(2)]-L-glutamine was ∼5% and the initial (13)C signal to noise ratio was ∼100:1. Glutamate was detected within seconds after the injection of hyperpolarized glutamine into the cells. The ratio of glutamate to glutamine was very high, indicating rapid conversion to glutamate. Similar cell uptake studies using [(3)H]-L-glutamine also demonstrated cell uptakes higher than that of [(18)F]fluorodeoxyglucose. CONCLUSION: We are reporting the first example of using specifically deuterated [5-(13)C-4-(2)H(2)]-L-glutamine in conjunction with hyperpolarized MRS for studying "glutaminolysis" in proliferating tumor cells.
Wenchao Qu; Zhihao Zha; Brian P Lieberman; Anthony Mancuso; Mathew Stetz; Rahim Rizzi; Karl Ploessl; David Wise; Craig Thompson; Hank F Kung
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-7
Journal Detail:
Title:  Academic radiology     Volume:  -     ISSN:  1878-4046     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9440159     Medline TA:  Acad Radiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.
Department of Radiology, University of Pennsylvania, 3700 Market Street, Suite 305, Philadelphia, PA 19104.
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