Abstract 6165: Early detection of pancreatic cancer by hyperpolarized magnetic resonance
Authors: Smith Paytience L. , Enriquez José S. , Howell Rian , Roux Olivereen Le , Pudakalakatti Shivanand , Dutta Prasanta , Mcallister Florencia , Bhattacharya Pratip 
Published: March 2024

Abstract
Introduction: Pancreatic cancer is difficult to diagnose due to its asymptomatic presentation at early stages. Therefore, there is an unmet need for non-invasive imaging markers that can help identify the aggressive pancreatic lesions at an early time point. One of the most promising imaging biomarkers is the conversion of hyperpolarized (HP) pyruvate to lactate1-3. With HP metabolic imaging, the conversion will be monitored among different premalignant models at different timepoints as well as tested against pancreatitis, a known confounder of pancreatic cancer in the clinic.
Methods: HP [1-13C]pyruvate Magnetic Resonance Spectroscopy (MRS) was employed to study the metabolic processes in tamoxifen inducible genetically engineered mouse models (P48CreERT2;LSL-KrasG12D(iKC)) with pre-invasive pancreatic intraepithelial neoplasia (PanIN) precursor lesions, invasive pancreatic cancer model (P48CreERT2;LSL-KrasG12D; LSL-p53R172H (iKPC)) and control animals (P48CreERT2 (iC)) at 7T Bruker MRI scanner. These mice were imaged before tamoxifen induction at 10-, 20-, and 30-weeks post induction. For the pancreatitis model, iC and iKC mice they were treated with caerulein for three weeks, 7 weeks after tamoxifen induction. The pancreatitis mice were imaged 24 hours after the last caerulein injection.
Results/Discussion: HP lactate-to-pyruvate ratio is increased in the cancer models compared to the control model. In the iKPC mouse model, at the 20-week post induction imaging there was a significant increase of the lactate-to-pyruvate ratio compared to the 10-weektime point after induction. The 20-week iKPC time point ratio compared to the iKC and control mouse models was significantly higher, indicating the aggressive nature of the disease. Even in the iKC model there is a slight increase
of the lactate-to-pyruvate ratio at 20-weeks post induction compared to both previous time points, pre-induction and 10-week. No change in the lactate-to-pyruvate ratio was not observed with the pancreatitis phenotype. In the future, we plan on imaging at earlier timepoints or at smaller intervals in the iKPC model, to observe the exact moment the metabolism switches to lactate.
Conclusion: Our data demonstrates that the metabolic flux to lactate is only increasing in the premalignant models of pancreatic cancer but not in the pancreatitis model, suggesting that the differentiation between early pancreatic cancer and pancreatitis can be achieved by hyperpolarized metabolic imaging. We are currently in the process of translating this in a clinical trial at MD Anderson Cancer Center.
Citation Format: Paytience L. Smith, José S. Enriquez, Rian Howell, Olivereen Le Roux, Shivanand Pudakalakatti, Prasanta Dutta, Florencia Mcallister, Pratip Bhattacharya. Early detection of pancreatic cancer by hyperpolarized magnetic resonance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6165.