Abstract
1260
Objectives: 18FDG PET can evaluate the start of tumor metabolism by monitoring glucose uptake. AcidoCEST MRI can evaluate extracellular pH (pHe) in the tumor microenvironment, which reflects lactic acid production at the end of the aerobic glycolysis pathway. Therefore, simultaneous PET/MRI has strong potential to provide a more comprehensive evaluation of tumor metabolism, especially tumor glycolysis. We proposed to employ simultaneous PET/MRI with 18FDG PET and acidoCEST MRI to evaluate the early response in a pancreatic tumor model treated with metformin.
Methods: A NuPET system from Cubresa, Inc., was placed in a 7T preclinical MRI scanner from Bruker BioSpin, Inc. This innovative imaging system allowed simultaneous PET/MRI scans to be routinely performed by a single operator within one hour. 18FDG PET studies were performed by intravenous injection of 4-12 MBq of 18FDG, which was allowed to circulate for 45 minutes in a flank model of MiaPACa-2 pancreatic cancer. Four CEST MR image sets were acquired, and 200 µL of 370 mgI/kg iopamidol was injected iv, followed by a 400 µL/hr infusion of agent during acquisition of six CEST MR image sets. PET images were processed with software provided by Cubresa. CEST MR images were processed with Matlab (Mathworks Inc.) . Post-processing analysis was performed with VivoQuant (inviCRO Inc.) to overlay PET and MR images.
Results: AcidoCEST MRI showed that metformin decreased tumor pHe relative to pre-treatment (p<0.02). This result was unexpected, because a decrease in tumor metabolism caused by therapy would be expected to decrease lactic acid production and therefore increase tumor pHe. Furthermore, vehicle-treated mice also showed a minor decrease in tumor pHe after treatment, indicating that tumor metabolism increased in this tumor model over time, further complicating the interpretation of the acidoCEST MRI results with metformin treatment. For comparison, PET showed that metformin decreased 18FDG uptake in tumors (p<0.002), indicating a therapy-induced decrease in tumor metabolism. Therefore, the decrease in tumor pHe was attributed to a decrease in aerobic respiration within mitochondria, which rerouted glucose metabolism to glycolysis that increased lactic acid production.
Conclusions: This study demonstrated that simultaneous PET/MRI improves interrogation of therapy-induced changes in tumor metabolism. If we only performed acidoCEST MRI, we may have incorrectly conlcuded that the drug enhanced metabolism. If we only performed 18FDG PET, we would not have been able to evaluate the rerouting of tumor cell metabolism caused by metformin.
