Nuclear spin hyperpolarization of pyruvate enables longitudinal monitoring of treatment response in intestinal tumor organoids

Colorectal cancer, a leading cause of death in the Western world, is increasingly affecting younger populations. The Warburg effect, characterized by enhanced lactate production, is a hallmark of this cancer type. While ¹⁸ F-FDG PET-CT is commonly used for diagnosis, magnetic resonance imaging (MRI) offers higher spatial and chemical resolution without the drawbacks of radiation. However, MRI's low sensitivity has been a barrier to real-time metabolic imaging, hence implementation into clinical practice. Hyperpolarization has significantly boosted NMR sensitivity, enabling detailed metabolic studies in vivo. This study utilizes hyperpolarized [1- ¹³ C]pyruvate with dissolution dynamic nuclear polarization (dDNP) to non-invasively monitor metabolic changes in intestinal organoids from a genetically defined mouse model of spontaneous carcinogenesis ( Rnaseh2b/Xbp1 ^ΔIEC ) with a previously established targeted therapeutic intervention (mTOR inhibition by rapamycin). Hyperpolarized NMR revealed a significant reduction in lactate production in rapamycin-treated organoids, indicating suppressed metabolic activity. This method also detected alanine and bicarbonate metabolism, highlighting its sensitivity. Unlike traditional methods that destroy cellular integrity, hyperpolarization enables repetitive, non-invasive metabolic assessments, bridging the gap between preclinical and clinical applications and affirming the method's potential for targeted metabolic imaging as a novel diagnostic and treatment control approach in cancer medicine.