Abstract 4172: Multi-parametric characterization of an experimental model of cancer cachexia

Abstract

Abstract Cachexia is a complex syndrome that is characterized by a massive loss of adipose tissue and skeletal mass. It is encountered in up to 50% of cancer patients and accounts for more than 20% of cancer related deaths. Currently, there is no known cure for cachexia, since mechanisms underlying its manifestation are not defined clearly enough to design effective therapeutic strategies. Here we have used magnetic resonance imaging (MRI) to characterize the vascular properties of cachectic vs. non-cachectic tumors. We have also analyzed the glucose metabolism of these tumors by using [18F]fluorodeoxyglucose (FDG) with positron emission tomography (PET). These studies will provide further insight into the cachectic phenotype that can be used to design treatments to arrest or reverse this condition. We used cachectic (MAC16) and non-cachectic (MAC13) murine colon adenocarcinoma tumors. The cell lines, originally from Dr. Tisdale's laboratory, were obtained from Dr. Sidransky with Dr. Tisdale's permission. Approximately 2 × 106 cells were inoculated in the flank of male SCID mice. MRI studies were performed on a 4.7T Bruker Avance spectrometer. Mice were anesthetized with an i.p. injection of ketamine and acepromazine. For vascular imaging, the tail vein was catheterized before placing the animal in the spectrometer. Multislice relaxation rate maps were obtained by a saturation recovery method combined with fast T1 SNAPSHOT-FLASH imaging. An M0 map with a recovery delay of 7 s was acquired from four 1 mm thick slices through the tumor followed by corresponding images obtained with three relaxation delays (100 ms, 500 ms, and 1 s). The T1 maps were obtained before i.v. injection of albumin-GdDTPA and repeated over a 21 minute period. For PET imaging, mice fasted overnight were injected with 0.2 mCi of FDG. At 60 min post injection, a 15 min static image was acquired over the tumors. Images were decay corrected and reconstructed using 2D OSEM. Cachectic MAC16 tumors induced extensive weight loss, unlike the non-cachectic MAC13 tumors. The difference in the weight of mice became significant within 2 weeks after inoculation. Mice with comparable tumor volumes were imaged 3 to 4 weeks after inoculation. While vascular volumes were not significantly different between the two groups, we did observe significantly lower permeability in the cachectic tumors. Consistent with the MRI data we found significantly lower levels of VEGF mRNA in quantitative-RT-PCR of tumor extracts of MAC16 tumors compared to MAC13 tumors but not in MAC16 cells compared to MAC13 cells. FDG PET imaging revealed increased glycolytic activity in a cachectic MAC16 tumor compared to a non-cachectic MAC13 tumor. These studies are part of our ongoing work to obtain a comprehensive characterization of the cachectic phenotype using noninvasive multi-modality imaging that will allow us to detect cancer-induced cachexia and identify new targets to prevent or reverse this condition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4172.