Abstract 5243: Value of 1H magnetic resonance spectroscopy compared with anatomical imaging in predicting response to standard chemotherapy and radiation in U87-MG-luc intracranial glioma model
Authors: Kaimal Vinod , Ziemke Matt , Trachet Erin , Elliott William , Leopold Wilbur R. , McConville Patrick 
Published: February 2011

Introduction: Luciferase enabled tumor cell lines are widely used for tracking orthotopic tumor burden in small animal models using bioluminescence imaging (BLI). Tumor burden estimated by MRI, while clinically relevant, may not correlate with patient survival. Tumor total (or phospho) choline has been shown to be an early indicator of tumor response to therapy measured using 1H (or 31P) magnetic resonance spectroscopy (MRS). In this study, correlation of response to therapy as measured by total choline (using 1H MRS) was compared with luciferase and MRI assessments of tumor burden, and lifespan.

Materials and methods: U87-MG-luc human glioma cells (106 cells in 10 μl) were implanted using a stereotax frame intracranially (2mm right lateral and 1mm anterior to the coronal suture at a depth of 2mm) in female CD1 nu/nu mice. On Day 27 post implant, intracranial tumor burden was characterized using BLI and animals were randomized into 3 groups-Group 1(n=9): vehicle controls saline, QDx5, 0.2ml/20g; Group 2 (n=9): BCNU QDx5, IV, 15mg/kg; Group 3 (n=6): 15 Gy radiation; (QDx5;2off)x2wks). Pre-treatment and 1 week post treatment scans were acquired using BLI (tumor burden), T2 weighted MRI (tumor volume) and water suppressed proton MR spectroscopy (spectra fitted to obtain total choline/NAA ratio). Additional BLI scans were performed weekly and animal lifespan was also recorded. For each parameter, mean and median were analyzed. Additionally, to assess the predictive power of each parameter, the animals on study were distributed into responder or non-responder categories using median lifespan in the control group as the threshold for response determination. Mean and medians for each parameter were then calculated separately for responders and non-responders.

Discussion: A Mann-Whitney rank sum test showed that the difference in median survival in both the treated groups was significantly different from controls, which had a median lifespan of 37.5 days. BCNU treatment (Group 2, p=0.021) was moderately active, resulting in a 5.5 day improvement in median lifespan. Radiation treatment (Group 3, p=0.003) was highly active, resulting in an 18.5 day improvement in median lifespan. Anatomical MRI determined tumor volumes and tumor luciferase signals at 1 week post treatment start were predictive of group median lifespan in Groups 2 and 3. Cho/NAA ratio at 1 week post-treatment start also correlated with response for Groups 2 and 3, but was less sensitive than the anatomically derived parameters. The secondary analysis based on response category revealed results consistent with the group mean and median analyses for all 3 parameters.

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 5243.