Towards Real-time Metabolic Profiling of Cancer with Hyperpolarized Succinate
Niki M. Zacharias1,2, Christopher R. McCullough1, Shawn Wagner3, Napapon Sailasuta4, Henry R. Chan4, Youngbok Lee1,5, Jingzhe Hu1,2, William H. Perman6, Cameron Henneberg4, Brian D. Ross4 and Pratip Bhattacharya1*
- *Corresponding Author:
- Pratip Bhattacharya
Department of Cancer Systems Imaging
University of Texas MD Anderson Cancer Center
1881 East Road, Unit 1907, Houston
E-mail: [email protected]
Received date: December 09, 2015; Accepted date: January 08, 2016; Published date: January 11, 2016
Citation: Zacharias NM, McCullough CR, Wagner S, Sailasuta N, Chan HR, et al. (2016) Towards Real-time Metabolic Profiling of Cancer with Hyperpolarized Succinate. J Mol Imag Dynamic 6:123. doi:10.4172/2155-9937.1000123
Copyright: © 2016 Zacharias NM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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 13C 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 T1 values, low toxicity and high water solubility. However, succinate and its derivative DES are metabolized robustly by RENCA but not by the other cancer models. Our results underscore the heterogeneity of cancer cells and the role cellular uptake plays in hyperpolarized metabolic spectroscopy.