Abstract 3050: Imaging tissue extracellular pH for the differential diagnosis of coccidioidomycosis and lung cancer

Abstract

Abstract Introduction: Our objective was to determine whether acidoCEST MRI—a novel, non-invasive MRI method that measures extracellular pH (pHe)—can differentiate between lung tumors and coccidioidomycosis (valley fever) granulomas within in vivo mouse models of lung cancer and valley fever. Methods: To develop a spontaneous murine lung tumor model, A/J mice received orthotopic injections of urethane to induce formation of lung adenocarcinomas. The Valley Fever Center for Excellence at the University of Arizona infected SW mice with a BSL 2-compatible mutant Coccidioides strain, Δcps1, to develop our preclinical valley fever model. All scans were performed with a Bruker BioSpin 7T MRI system. For all MRI scans, mice were anesthetized with 2.0% isofluorane, respiration and body temperature were monitoreduring scans, and body temperature was maintained at 37 °C. Respiration-triggering (gating) was used in all imaging sequences to compensate for motion artifacts in the lung. For optimal gating, the mouse's respiration rate was maintained at < 50 breaths per minute. Each mouse was scanned with acidoCEST MRI using 370 mg/mL Iopamidol (200 μL IV bolus, 400 μL/hr IV infusion). AcidoCEST MRI (3.5 μT, 300 ms imaging time, 6000 ms presaturation pulse) was performed according to previously published methods, updated with improved respiration gating. For acidoCEST MRI, the saturation pulse continued until terminated by the gating trigger. Spatial pHe maps of tumor and granuloma ROI were produced using Bloch fitting in Matlab 2014a. Average lesion pHe and iopamidol concentration we also recorded. Results: AcidoCEST MRI was successfully applied to the in vivo imaging of murine lung tumors and coccidioidomycosis granulomas. Lung tumors demonstrated successful uptake of the iopamidol contrast agent, with an average concentration of approximately 40 mM. pHe values in the tumor ROI ranged from 6.5 to 7.2 with an average value of 6.64. Granulomas demonstrated successful uptake of iopamidol with an average concentration of about 75 mM. pHe values in granulomas ranged from 7.2 to 7.4 with an average value of 7.29. Conclusion: AcidoCEST MRI may be used to quantify the pHe of murine lung tumors and coccidioidomycosis granulomas in vivo. Our results show that pHe is a promising biomarker for the differential diagnosis of coccidioidomycosis and lung cancer. Citation Format: Leila Renee Lindeman, Edward A. Randtke, Lisa F. Shubitz, Christine M. Howison, Kyle M. Jones, Mark D. Pagel. Imaging tissue extracellular pH for the differential diagnosis of coccidioidomycosis and lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3050.