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Towards Real-time Metabolic Profiling of Cancer with Hyperpolarized Succinate
Niki M Zacharias1, Christopher R McCullough2, Shawn Wagner3
1Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, USA; Department of Bioengineering, Rice University, 6100 Main Street, Houston, USA.
Journal of Molecular Imaging & Dynamics
|August 23, 2016
Summary
Hyperpolarized succinate (SUC) and diethyl succinate (DES) enable real-time Krebs cycle imaging in cancer models. While promising, metabolism varies significantly across cancer types, highlighting cellular heterogeneity.
Area of Science:
- Metabolic Imaging
- Cancer Research
- Biochemistry
Background:
- The mitochondrial Krebs cycle is crucial for cellular energy production, generating ~90% of adenosine triphosphate.
- Dysfunction and mutations in the Krebs cycle are implicated in various cancers and diseases.
- Real-time interrogation of metabolic pathways in vivo is essential for understanding cancer biology.
Purpose of the Study:
- To design and synthesize hyperpolarized carbon-13 labeled succinate (SUC) and diethyl succinate (DES).
- To investigate the real-time metabolism of SUC and DES within the Krebs cycle in cancer animal models.
- To assess the potential of these hyperpolarized agents for in vivo metabolic imaging of cancer.
Main Methods:
- Hyperpolarized SUC and DES were generated using Parahydrogen Induced Polarization (PHIP) via hydrogenation of fumarate precursors.
- Metabolism of SUC and DES was studied in five allograft cancer models: breast (4T1), Renal Cell Carcinoma (RENCA), colon (CT26), and two lymphomas (NSO, A20).
- Carbon-13 Fast Imaging with Steady Precession (FISP) imaging was used to observe biodistribution and metabolic conversion in vivo.
Main Results:
- Achieved hyperpolarization levels of 8 ± 2% for SUC and 2.1 ± 0.6% for DES.
- Metabolism of hyperpolarized SUC and DES in the Krebs cycle was observable in animals within 5 seconds post-injection.
- Significant differences in the uptake and conversion rates of SUC and DES were observed across different cancer cell types both in vitro and in vivo.
Conclusions:
- Hyperpolarized DES and SUC exhibit favorable properties for in vivo metabolic imaging, including high polarization, suitable T1 values, low toxicity, and good water solubility.
- Robust metabolism of SUC and DES was observed in Renal Cell Carcinoma (RENCA) but not in the other tested cancer models.
- These findings underscore the significant heterogeneity among cancer cells and emphasize the critical role of cellular uptake in hyperpolarized metabolic spectroscopy applications.
