Towards Real-time Metabolic Profiling of Cancer with Hyperpolarized Succinate.
| Autor: | Zacharias NM; Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, USA; Department of Bioengineering, Rice University, 6100 Main Street, Houston, USA., McCullough CR; Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, USA., Wagner S; Department of Biomedical Sciences, Cedars-Sinai, Los Angeles, USA., Sailasuta N; Enhanced Magnetic Resonance Laboratories, Huntington Medical Research Institutes, Pasadena, USA., Chan HR; Enhanced Magnetic Resonance Laboratories, Huntington Medical Research Institutes, Pasadena, USA., Lee Y; Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, USA; Department of Applied Chemistry, Hanyang University, Ansan, Korea., Hu J; Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, USA; Department of Bioengineering, Rice University, 6100 Main Street, Houston, USA., Perman WH; Department of Radiology, School of Medicine Saint Louis University, St. Louis, USA., Henneberg C; Enhanced Magnetic Resonance Laboratories, Huntington Medical Research Institutes, Pasadena, USA., Ross BD; Enhanced Magnetic Resonance Laboratories, Huntington Medical Research Institutes, Pasadena, USA., Bhattacharya P; Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of molecular imaging & dynamics [J Mol Imaging Dyn] 2016 Jun; Vol. 6 (1). Date of Electronic Publication: 2016 Jan 11. |
| DOI: | 10.4172/2155-9937.1000123 |
| Abstrakt: | Purpose: The energy-yielding mitochondrial Krebs cycle has been shown in many cancers and other diseases to be inhibited or mutated. In most cells, the Krebs cycle with oxidative phosphorylation generates approximately 90% of the adenosine triphosphate in the cell. We designed and hyperpolarized carbon-13 labeled succinate (SUC) and its derivative diethyl succinate (DES) to interrogate the Krebs cycle in real-time in cancer animal models. Procedures: Using Parahydrogen Induced Polarization (PHIP), we generated hyperpolarized SUC and DES by hydrogenating their respective fumarate precursors. DES and SUC metabolism was studied in five cancer allograft animal models: breast (4T1), Renal Cell Carcinoma (RENCA), colon (CT26), lymphoma NSO, and lymphoma A20. Results: The extent of hyperpolarization was 8 ± 2% for SUC and 2.1 ± 0.6% for DES. The metabolism of DES and SUC in the Krebs cycle could be followed in animals 5 s after tail vein injection. The biodistribution of the compounds was observed using 13 C FISP imaging. We observed significant differences in uptake and conversion of both compounds in different cell types both in vivo and in vitro . Conclusion: With hyperpolarized DES and SUC, we are able to meet many of the requirements for a useable in vivo metabolic imaging compound - high polarization, relatively long T |
| Databáze: | MEDLINE |
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