Assessing the treatment of pancreatic ductal adenocarcinoma by deuterium metabolic imaging: a preclinical study

PURPOSE: To evaluate the utility of Deuterium Metabolic Imaging (DMI) as a tool for monitoring disease progression and assessing the therapeutic efficacy of cyclophosphamide in pancreatic ductal adenocarcinoma (PDAC). METHODS: The study utilized C57BL mice implanted with a PDAC model, and separated into two experimental groups: One cohort served as an untreated control, while the second was treated with the chemotherapeutic agent cyclophosphamide (CP). Metabolic mapping for the two cohorts was performed over the course of weeks using 2H MRSI at 15.2T, tracking the metabolic pathway of deuterated glucose as it converts by the PDAC into lactate. RESULTS: CP administration led to a significant reduction in tumor growth and improved survival rates compared to the control group. Tumor growth rates for the untreated, control group, showed a strong inverse correlation for glucose's uptake and a strong direct correlation with the glucose-to-lactate conversion rates as seen by DMI. CP treatment disrupted both these correlations: Post-treatment, tumor growth rates became statistically uncorrelated with either glucose consumption or lactate production which, when normalized for tumor size, remained relatively constant during the treatment period. CONCLUSION: The study demonstrates that CP treatment fundamentally alters the metabolic kinetics of glucose in PDAC tumors, inducing disruptions in metabolic correlations that may serve for distinguishing therapeutic success from failure.