Detection of Metabolic Changes using Hyperpolarized 13C MRI in a Negative 18F-FDG PET Rat Brain Cancer Model

1177 Objectives: Hyperpolarized [1-13C]pyruvate MRI and 18F-FDG PET imaging are two distinctive imaging techniques that report on complementary aspects of the intracellular glucose metabolism. Low grade human gliomas are known to be 18F-FDG negative and focus have recently been on developing new imaging biomarkers that can identify and characterize these types of tumors. In this study we compared hyperpolarized [1-13C]pyruvate MRI and 18F-FDG PET Imaging in a rat model of spontaneous slow growing N-ethyl-N-nitrosourea induced gliomas 1. Methods: N-nitroso-N-ethylurea (ENU) a carcinogen chemical, was injected into female rats during pregnancy, which result in birth of rats that spontaneous develops tumors in neuronal tissue (eg. gliomas)2. ENU rats (n = 6, 110-120 days old) with suspected gliomas were anesthetized with isoflurane and scanned in a GE 3T Signa scanner. Anatomical images as well as T2 weighted images (dual FSE) were acquired prior to 13C MRI using hyperpolarized [1-13C]pyruvate (125mM, 7s bolus inj.). The 13C MRI signals were acquired using a 13C surface coil (15mm diam.) and a 16x16 phase encoded FID-CSI sequence (FA: 100, TR=75ms, FOV: 64mm, special res: 4x4x5mm). The 13C MRI acquisition was followed by a gadolinium enhanced MRI scan (T1-weighted SE). 1-2 days later the rats were imaged in a micro-PET scanner (Siemens Inveon D-PET). 18F-FDG (1mCi in saline) was injected iv. followed by 1 hour of dynamic acquisition (3D TF iterative OSEM algorithm). All rats were fasted 18-20h prior to the PET scan. The Gd-enhanced MRIs were used for co-registration of 13C MRI and PET images and for identifying tumor regions of interest (ROIs). Visualization of 18F tracer uptake, ROI identification and analysis of signal differences were performed using PMOD. Tumor and tissue TACs were normalized to injected dose (%ID/g assuming 1g/ml). Normalized uptake of 18F-FDG at 60 min was used for comparison between groups and in the tumor ROIs in contrast to normal-appearing brain ROIs. Hyperpolarized 13C metabolic maps of pyruvate, lactate and bicarbonate and 13C ROI analysis, were performed in MATLAB by integrating the area under the curve of the 13C metabolic peaks. After the scanning the rats were euthanized, and their brain perfused and histology (H&E staining) was performed on selected brain slices corresponding to the MRI images. Results: The MRI’s revealed tumors in 5 out of 6 animals and 2 animals had more than 1 tumor. The histology correlated well with T2 weighted MRI’s (Fig. 1D). 5 out of 7 tumors were negative on the Gd-enhanced T1-weighted MRIs. PET imaging showed no or poor enhancement of 18F-FDG in the chosen tumor ROI’s compared to normal appearing brain regions (Fig. 1A and 1E). Hyperpolarized 13C MRI however did show metabolic differences. The Lac/Bic signal was increased in 5 out of 6 tumors (Fig. 1F). Conclusions: The present study demonstrates that hyperpolarized 13C MRS potentially can be used to identify and characterize gliomas that are 18F-FDG negative. The Lac/Bic imaging marker is interesting because it reports on the ratio between increased glycolysis (Warburg effect) and the more ATP favorable oxidative phosphorylation inside the cells3. Further histological analysis will be performed to get better understanding how the metabolic differences correlate with the proliferative state of the tumor. Acknowledgements NIH grants R01CA176836, R01EB019018, P41EB01589, S10OD012283, S10OD018130-01 GE HealthcareLucas Foundation References1. Druckrey H, Ivankovic S, Preussmann R. Nature 210:1378-1379, 1966 2. Jang T, Sathy B, Hsu YH, Merchant M, Recht B, Chang C, Recht L. J Neurosurg108:782-90, 20083. 3. Park JM, Spielman D, Josan S, Jang T, Merchant M, Hurd RE, Mayer D and Recht LD. NMR Biomed. 29(5):650-9, 2016