研究目的
To interrogate the Krebs cycle in real-time in cancer animal models using hyperpolarized carbon-13 labeled succinate and its derivative diethyl succinate.
研究成果
Hyperpolarized DES and SUC are effective for real-time metabolic imaging in specific cancer models, demonstrating high polarization, long T1 values, low toxicity, and good solubility. However, metabolism is robust only in RENCA tumors, highlighting cancer heterogeneity and the critical role of cellular uptake. Future work should explore other succinate derivatives for broader utility.
研究不足
The study has limitations in precise quantification of metabolic flux due to T1 decay and magnetization usage. The variability in DES uptake in vitro and the specificity of uptake to certain cancer types (e.g., RENCA) limit broad applicability. The techniques require specialized equipment and may not be easily translatable to all cancer models.
1：Experimental Design and Method Selection:
The study used Parahydrogen Induced Polarization (PHIP) to hyperpolarize succinate (SUC) and diethyl succinate (DES) by hydrogenating fumarate precursors. Real-time metabolic profiling was conducted using Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) on a
2：7 T MR scanner. Sample Selection and Data Sources:
Five cancer allograft animal models were used: breast (4T1), Renal Cell Carcinoma (RENCA), colon (CT26), lymphoma NSO, and lymphoma A
3：Samples included hyperpolarized agents injected via tail vein. List of Experimental Equipment and Materials:
A
4：7 T MR scanner (Bruker Avance), home-built reaction chamber for hydrogenation, parahydrogen gas, rhodium catalyst, fumarate precursors (e.g., 1-13C fumarate-d2 from Cambridge Isotope Laboratories), various coils (e.g., 25 mm multi-turn 1H-13C homemade loop coil, full body 1H/13C dual tuned volume coil from Doty Scientific Inc.), and software (Paravision 2, 3DiCSI). Experimental Procedures and Operational Workflow:
Hydrogenation was performed at specific temperatures and pressures (e.g., 60°C, 12 bar H2 for DES; 62°C, 10 bar H2 for SUC). Radiofrequency pulses were applied to transfer polarization. Hyperpolarized agents (
5：5 ml) were injected into mice, and MRS/MRI was conducted post-injection with sequences like FISP and CSI. Data acquisition involved multiple averages and repetitions over time. Data Analysis Methods:
Data were analyzed using spectroscopy and imaging techniques, with chemical shift referencing to acetate phantoms. Signal decay and metabolic flux rates were estimated, considering T1 relaxation times. Statistical analysis included mean and standard deviation calculations.
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