(1) Improving tumor diagnoses based on imaging metabolism with PET/MRI: Our goal is to improve cancer diagnoses using tumor acidosis as a noninvasive, longitudinal biomarker for cancer imaging. Glycolytic metabolism is upregulated in many solid tumors, known as the Warburg effect, which increases lactic acid production and causes acidosis of the tumor microenvironment. Other pathologies such as fibrosis, inflammation, and infection produce little or no tissue acidosis. Therefore, imaging extracellular pH (pHe) can differentiate cancer from non-cancerous pathologies. In addition, [F18]FDG PET can be used to differentiate tumors from infections; [F18]FET PET has been used to differentiate tumors from inflammation; Ga68 agents are currently under development that can evaluate tissue fibrosis. The combination of PET with acidoCEST MRI has strong potential to further improve tumor diagnoses.
(2) Improving cancer immunotherapy based on imaging tumor metabolism with PET/MRI: Extracellular acidosis in the tumor microenvironment causes resistance to immunotherapy. We are evaluating acidosis neutralization treatments that inhibits extracellular acidosis and reduces resistance to immunotherapy. To support these evaluations, we are using our innovative imaging method, acidoCEST MRI, to monitor tumor acidosis during acidosis neutralizing treatments with immunotherapy. To further improve our imaging evaluations, we will perform simultaneous PET/MRI studies with mouse tumor models to compare acidoCEST MRI with FDG PET, where FDG PET can evaluate tumor viability. This combination will be used to determine if acidosis neutralization only changes tumor pHe without affecting tumor viability, or if acidosis neutralization changes tumor pHe and also contributes an anti-cancer effect. Together, simultaneous PET/MRI provides a key technology for imaging tumor metabolism that can improve cancer immunotherapy.
(3) Improving assessments of tumor acidosis with new PET/MRI contrast agents: Our goal is to quantitatively measure extracellular pH (pHe) in the tumor microenvironment to assess tumor acidosis. These assessments can be used to improve evaluations of solid tumors, and to aid in predicting the response to immunotherapy before the treatment is initiated. To meet this goal, we are developing PET/MRI contrast agents that can quantitatively measure pHe, and apply these agents during simultaneous PET/MRI studies in mouse models of human cancers. Dynamic changes in the relaxation-based MR image contrast are sensitive to tumor pHe as well as the concentration of the agent in tumor tissue, while the PET image can be used to measure the concentration of the agent in the tumor. Therefore, the PET results can be used to account for the effect of concentration on MR image contrast, which can improve the quantitative measurement of tumor pHe. Our deliverable is a fundamentally new class of contrast agents for molecular imaging with PET/MRI. As a longer term goal, our PET/MRI contrast agents have outstanding potential for clinical translation, which will provide a transformative “game changing technology” for clinical PET/MRI.