Effects on Tumor Metabolism In Repetitive MRI Measurements Using Hyperpolarized Pyruvate
Abstract
Purpose
To investigate the dependence of tumor metabolism on hyperpolarized (HP) pyruvate concentration, administration order, and time interval in repeated MRI measurements.
Methods
Aliquots of 13C pyruvic acid were polarized using Polaris (NVision Imaging Technologies) or HyperSense (Oxford Instruments). Following dissolution, two HP pyruvate solutions were prepared: 40mM (diluted with saline) and 80mM (undiluted), and 200μL of each was administered via tail-vein catheter accordingly. Ten anaplastic thyroid cancer tumor-bearing mice (Hth83 cells) were imaged under IACUC-approved protocols. Three mice received 40mM dose administered first followed by 80mM after 0.5-hour interval (Polaris polarized) within the same imaging session. Four mice received 40mM first followed by 80mM after 24 hours (HyperSense polarized). Three mice received 80mM first followed by 40mM after 24 hours (HyperSense polarized). MRI experiments were performed on a 7T Biospec Bruker system. HP metabolites signals were acquired using single-shot flyback EPI readout with spectral-spatial excitation. Image reconstruction and data analysis were performed in MATLAB R2024b (MathWorks, Natick, MA). A one-compartment, two-chemical-pool pharmacokinetic model was used to fit kPL within the thyroid tumor region. One-way Anova was employed for statistical analysis.
Results
Two HP pyruvate injections exhibited consistent tendency within the same animal: 40mM consistently yielded higher kPL than 80mM across all groups (0.5-hour interval, 24-hour interval and 24-hour interval with reverse injection order). Additionally, the difference in kPL (ΔkPL) between the 40mM and 80mM injection within the same animal was not significantly affected by injection order or time interval.
Conclusion
We investigated tumor-region kPL in mice following successive HP pyruvate injections with varying concentration, administration order, and time interval. Our results show that kPL was consistently higher for the 40mM injection than for the 80mM injection and was robust to injection order and time interval, indicating that consecutive HP pyruvate injections provide reproducible metabolic measurements in repetitive studies.