William H. Perman
Tanzania
Research Article
Towards Real-time Metabolic Profiling of Cancer with Hyperpolarized Succinate
Author(s): Niki M. Zacharias, Christopher R. McCullough, Shawn Wagner, Napapon Sailasuta, Henry R. Chan, Youngbok Lee, Jingzhe Hu, William H. Perman, Cameron Henneberg, Brian D. Ross and Pratip BhattacharyaNiki M. Zacharias, Christopher R. McCullough, Shawn Wagner, Napapon Sailasuta, Henry R. Chan, Youngbok Lee, Jingzhe Hu, William H. Perman, Cameron Henneberg, Brian D. Ross and Pratip Bhattacharya
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%.. View More»
