Overhauser Enhanced Magnetic Resonance Imaging (OMRI)

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

Project Summary: a) Multimodal imaging of tumor physiology and metabolism: Tumor metabolic profile using 13C labeled pyruvate has been shown to be useful in profiling tissue metabolism in terms of oxidative phosphorylation (OxPhos) vs aerobic glycolysis using hyperpolarized MRI (HP MRI). The uptake of pyruvate is required in both cases which proceeds through the monocarboxylate transporters. Currently the hypermetabolic activity in the clinic to detect malignancy is by the use of 18F labeled deoxyglucose (FDG) with Positron emission tomography (PET). FDG uptake proceeds by glucose transporters and converted to cellularly entrapped FDG-6-phosphate mediated by hexokinase. Since both hyperpolarized MRI and PET report on hypermetabolism using different transporters and different enzymes, we conducted a study on three previously characterized tumors with HP MRI and FDG/PET. The results show a good correspondence between HP MRI and FDG PET validating the chemical shift imaging modality. Further, the HP MRI provided additional information than PET in terms of showing the contribution of OxPhos as well as aerobic glycolysis. b) Molecular imaging assessment of photoimmunotherapy: Photoimmunotherapy (PIT) using the near infra red (NIR) absorbing dye IR 700 linked with antibodies targeting the EGFR receptor has shown remarkable efficacy in pre-clinical models tumors expressing EGFR. Based on these results, clinical studies have started with promising results. The mechanistic aspects of tumor cell killing in vitro and in vivo has been studied using HP MRI, T2 weighted MRI and photoacoustic imaging. Results showed that the in vivo cell killing proceeds by necrotic death immediately post NIR PIT. c) Prostate: Two prostate cancer cells, DU-145 and PC3 were profiled metabolically using HP MRI and 1H MRSI in tumors implanted in mice. While HP MRI studies showed that DU 145 tumor implants were more glycolytic than PC3, steady state MRI assessment of lactate levels showed no difference between the two tumor implants. Treatment with an LDHA inhibitor Fx 11 showed that the DU-145 tumors responded better compared to PC3 implants. These studies showed that HP MRI has sensitivity to profile tumors and select for appropriate therapy. d) Clinical Imaging. i) Pulse sequences and coils for human studies have been tested.