Clinically Translatable Hyperpolarized ¹³C Bicarbonate pH Imaging Method for Use in Prostate Cancer

Area of Science:

• Oncology
• Medical Imaging
• Biochemistry

Background:

• Solid tumors, including prostate cancer (PCa), often exhibit an acidic tumor microenvironment (pH 6.5-7.2) due to factors like poor perfusion and high metabolic activity.
• Decreased tumor extracellular pH correlates with disease progression in preclinical PCa models, suggesting its potential as an imaging biomarker for aggressive disease.

Purpose of the Study:

• To develop and clinically translate a hyperpolarized carbon-13 MRI method for imaging tumor extracellular pH (pHe) in prostate cancer.
• To establish pH imaging as a tool for the detection and risk stratification of PCa.

Main Methods:

• Development of a hyperpolarized (HP) 1,2-glycerol carbonate (carbonyl-13C) based MRI method for pHe imaging.
• Utilized base-catalyzed hydrolysis to generate HP 13CO32-, which is converted to HP H13CO3- for in vivo administration.
• Overcame polarization loss issues in clinical polarizer systems and customized reaction apparatus for clinical application.

Main Results:

• Successfully produced a highly polarized, safe, and clinically translatable HP H13CO3- contrast agent.
• Preclinical studies demonstrated reliable and accurate measurement of kidney and prostate tumor acidification.
• Methodology supported an Investigational New Drug application, paving the way for human trials.

Conclusions:

• The developed HP 13C MRI method is ready for clinical implementation in human trials for prostate cancer.
• This pH imaging technique holds promise for improving the detection, risk stratification, and overall management of PCa.
• Imaging tumor extracellular pH offers a novel biomarker for assessing disease aggressiveness.