Integrated Precision Imaging for Immune-related Adverse Events: Hyperpolarized 13C-MRI and Metabolomics

Immune-related adverse events (irAEs) have become clinical challenges with the exponential increase in the use of immune checkpoint inhibitors (ICIs) in medical oncology. irAEs can be fulminant and fatal, requiring personalized management. Early prediction and accurate risk categorization of irAEs are urgently needed to tailor patient management. Glucose metabolism in the spleen may reflect immune activity and has been used to predict tumor response to ICIs. Since the underlying mechanism of irAEs is similar to ICIs tumor response, the splenic metabolism is a potential biomarker for irAEs.

This project is novel because it aims to investigate irAEs from the perspective of metabolism by integrating hyperpolarized (HP) 13C-MRI, metabolomics, and MR fingerprinting (MRF). HP 13C-MRI is a new non-invasive, real-time dynamic imaging technique used to detect the metabolic flux in vivo. Dynamic nuclear polarization (DNP) is a hyperpolarization technique that increases the signal of 13C-labeled probes by up to 50,000-fold. With DNP, [1-13C]pyruvate can be used to probe various metabolic pathways, including its conversion to lactate (anaerobic glycolysis), alanine (transamination), and bicarbonate (indirect marker for TCA cycle). These specific metabolic alterations have been used to characterize the functions of immune cells; thus, they may also reflect the splenic immune activity in patients with irAEs. Additionally, NMR-based metabolomics analyses of patients' serum and urine will provide a more global view of metabolic changes of whole human body. Furthermore, the observed metabolic alterations can be translated into multiparametric tissue properties obtained by MRF.

The investigator design a 3-year project with a non-randomized, two group assignment observational study design. This research will include 30 cancer patients receiving ICIs. Twenty patients experiencing acute phase irAEs (grade 2 or higher) and 10 patients not experiencing irAEs after 14 weeks of treatment will be recruited for this prospective single institutional study. A dedicated multidiscipline immune-oncologic board will screen patients who develop irAEs, which include colitis, endocrinopathy, hepatitis, pneumonitis, and skin toxicity. The diagnosis of the irAEs is determined by clinical history, laboratory values, standard-of-care imaging, and histopathologic features when biopsy is necessary. Participants eligible for this study will undergo investigative exams including HP 13C-MRI, metabolomics, and MRF.

The investigator hypothesize that the spleen immune activity interrogated using HP 13C-MRI can predict the occurrence of irAEs. Additionally, the level of splenic metabolic alterations based on HP 13C-MRI will be correlated to the clinical severity of irAEs, providing additional risk categorization for irAEs. Moreover, by establishing metabolic information and tissue characteristics obtained by MRF, the dynamic changes of immune activity may be monitored by the quantifiable and reproducible tissue properties. Finally, by combining HP 13C-MRI and metabolomics, the investigator will have a better understanding of the pathophysiology of irAEs from the perspective of metabolism, which may lead to the development of new therapy.