Introduction

Hyperpolarized ¹³C pyruvate MRI and ¹⁸F-FDG PET imaging are two distinctive imaging techniques that report on complementary aspects of intracellular glucose metabolism. Combining the two techniques may provide better insight in the metabolic processes that drives diseases such as cancer. In this study we compared hyperpolarized [1-¹³C]pyruvate MRI and ¹⁸F-FDG PET Imaging signals in a rat model of spontaneous slow growing glioma ¹.

Methods

N-ethyl-N-nitrosourea (ENU) a carcinogen chemical, was injected into female rats during pregnancy, which result in birth of rats that later spontaneous developed tumors in neuronal tissue including the brain (gliomas) ². Rats (n = 6, 450-550g, 110-120 days old) with suspected ENU gliomas were anesthetized with Isoflurane and scanned in a GE 3T Signa scanner with hyperpolarized [1-¹³C]pyruvate (125mM, 7s bolus injection). ¹³C MRI signals was acquired using a ¹³C surface coil (diam: 15mm) and a 16x16 phase encoded FID-CSI sequence (FA: 100, TR=75ms, FOV: 64mm, special resolution: 4x4x5mm). The ¹³C MRI was followed by a gadolinium enhanced MRI scan (T1-weighted spin echo). 1-2 days later the rats were imaged in a PET scanner (Siemens Inveon D-PET, microPET scanner). ¹⁸F-FDG (1mCi in saline) was injected iv. followed by 1 hour of dynamic PET acquisition. All rats were fasted for 18-20 hours prior to ¹⁸F-FDG injection. The Gd-enhanced T1-weighted MRIs were collected for co-registration of MR and PET images and for identifying tumor regions of interest (ROIs). Visualization of ¹⁸F radio tracer uptake, ROI identification and analysis of signal differences were performed using PMOD software (Version 3.7, PMOD Technologies, Zürich, Switzerland). Normalized uptake of ¹⁸F-FDG at 60 min was used for comparison between groups and in the tumor ROIs in contrast to the normal-appearing brain ROIs (figure 1). Hyperpolarized ¹³C metabolic maps of pyruvate, lactate and bicarbonate and ROI analysis, were performed in MATLAB by integrating the area under the curve of the ¹³C metabolic peaks.

Results

The Gd-enhanced T1-weighted MRIs revealed tumors in 5 out of 6 animals and 2 animals had more than 1 tumor. PET imaging showed no enhancement of ¹⁸F-FDG signal in the tumor regions compared to the contralateral normal appearing brain regions (FDG negative). Hyperpolarized ¹³C MRI however did show metabolic differences in all animals (Figure 1).

Discussion

Low grade human gliomas are known to be ¹⁸F-FDG negative and much focus have recently been on developing new radio tracers that can identify these types of tumors. The ENU rat model is a spontaneous and slow growing glioma model that mimics the growth pattern of many human gliomas. The present study suggests that hyperpolarized ¹³C MRS potentially may be used to identify and characterize 18F-FDG negative gliomas similar to the ENU tumors. The results from the metabolic imaging will be compared with histologic data to established if the metabolic differences correlate with the proliferative state of the tumor.