Abstract 4307: MRI characterization of OKN-007 efficacy in a preclinical pediatric glioma model

Abstract

Abstract High grade gliomas (HGG) are common primary CNS tumors in children. Here, we report the preliminary data about the efficacy of a nitrone compound, OKN-007 [Oklahoma Nitrone 007; a disulfonyl derivative of α-phenyl-tertbutyl nitrone (PBN)], in a preclinical pediatric HGG model (IC3752GBMV) by using Magnetic Resonance Imaging (MRI). The right cerebrum of eight week old male athymic nude mice was injected with IC3752GBMV pediatric HGG cells. The animals were divided in 2 groups: (A) untreated and (B) treated with OKN-007, which was given continuously (0.025% w/v) by drinking water after the tumors have reached volumes of 10-20 mm3. MRI was performed using a 7 Tesla Bruker BioSpin system and repeated weekly to access the tumor volumes. Diffusion-Weighted Imaging (DWI), Perfusion-Weighted Imaging (PWI), and Magnetic Resonance Spectroscopy (MRS) techniques were performed in both groups to evaluate the efficacy of OKN-007 in the pediatric cell lineage IC3752GBMV. The results of this study are preliminary and we are reporting here the data of only one animal of each group. For the OKN-007 treated group (88.58 mm3), the tumor volume was decreased when compared to the untreated group (139.3 mm3) at the last day point (day 51). Based on DWI, the ADC (Apparent Diffusion Coefficient) values (1x10-4 mm2/s) of the tumors normalized to contralateral brain were 0.949 for Group A, and 1.087 for Group B. The tumor of the OKN-007 treated animal had increased perfusion ratio (tumor/contralateral side of the brain) of 0.58 in comparison to the untreated control ratio of -5.28. The MRS data showed that the lipid (methylene)-to-creatine ratio was decreased in the pediatric glioma treated with OKN-007 versus the untreated tumor (14.89 and 23.75 respectively). This is the first report of evaluation of anti-cancer therapy efficacy of OKN-007 in a pediatric xenograft model by using DWI, PWI, and MRS techniques. Based on our preliminary results, DWI, PWI and MRS may provide some information useful in evaluating OKN-007 anti-cancer therapeutic response in pediatric HGG. OKN-007 decreased the tumor volume, and increased tumor perfusion rates, similar to what we found in a rat glioma model1. OKN-007 may also affect tumor metabolism in this pediatric HGG model, which was denoted by changes in the lipid (methylene)-to-creatine ratio. Similar results have been described previously in several different glioma models by our group2. In conclusion, the pediatric HGG IC3752GBMV model may facilitate biological studies and preclinical drug screenings for pediatric HGG. Furthermore, OKN-007 may be considered as a potential alternate and new therapy for pediatric HGG. This preliminary data will need to be repeated to confirm our findings. REFERENCES 1. Garteiser P. et al (2010). J Magn Reson Imaging. 31: 796-806. 2. Doblas S et al (2012). NMR Biomed.25:685-94. Note: This abstract was not presented at the meeting. Citation Format: Patricia Coutinho de Souza, Nataliya Smith, Charity Njoku, Debra Saunders, Krithika Balasubramanian, Rene Y. McNall, Xiao-Nan Li, Rheal A. Towner. MRI characterization of OKN-007 efficacy in a preclinical pediatric glioma model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4307. doi:10.1158/1538-7445.AM2014-4307