Abstract 4179: Magnetic resonance imaging and bioluminescence imaging for evaluating tumor burden in orthotopic glioblastoma
Authors: Guo Mingrui , Su Ruisong , Chor Jeff W H , Zhang Zheyan , Tan Mandy , Teo Xing Qi , Feng Haosheng , Lee Kuan J. , Hua Li , Zhang Longyun , Cai Jie , Mao Guanping , Wang Jingjing , Chng Keefe , Han Weiping , Guo Colin 
Published: March 2024

Abstract
Accurate monitoring of orthotopic tumors in oncological research is critical. While conventional surgical exposure method or imaging methods such as bioluminescence imaging (BLI), ultrasound imaging (US) and computed tomography (CT) have different advantages and limitations. Magnetic Resonance Imaging (MRI) offers a non-invasive modality with high sensitivity. This study compares BLI and MRI in tracking tumor progression, focusing on the human glioblastoma multiforme (GBM) orthotopic xenograft mouse model. To establish the GBM model, human glioblastoma cells U87 MG-luc, expressing firefly luciferase, were intracranially implanted in female BALB/c nude mice. In-life tumor growth was assessed longitudinally every 3-4 days using BLI (IVIS Lumina S5, PerkinElmer, US) and MRI (Bruker BioSpec 117/16, 11.7T ultra-high field scanner, Germany) with a T2-weighted sequence. Mice were randomized into two groups (n=8) based on the MRI-derived tumor volume and BLI signal on the 3rd day post inoculation. One day after grouping, each cohort received specific treatments: one with the standard vehicle control and the other with Temozolomide (TMZ) (10mg/kg, 5 days/week, oral gavage). This treatment lasted until day 21, after which whole brains were removed and tumors excised from surrounding normal tissue and weighed. The results from both BLI and MRI showed that the control group exhibited consistent tumor growth, while TMZ treatment significantly inhibited tumor growth by day 21. However, some differences were observed, particularly for small tumor size, with more accurate measurement with MRI compared to BLI. By day 7 (3 days post treatment), MRI indicated a Tumor Growth Inhibition (TGI) of 32.63%, whereas BLI indicated a 5.04% increase in the TMZ-treated group compared to the control group. From day 11 onwards, both methods demonstrated a TGI exceeding 70% with TMZ treatment. Moreover, there was a pronounced difference in tumor weight correlations: MRI assessments showed a strong correlation (R2=0.9967) with extracted tumor weights, whereas in contrast to BLI showed a weaker correlation (R2=0.5371). The lower correlation for BLI, could be explained by the hypoxia and necrosis commonly observed in larger tumors or after treatment leading to decrease of ATP and reduction of bioluminescence. BLI offers rapid 2D imaging but lacks precision in determining location and depth of GBM tumor. Moreover, it requires luciferase engineered cell lines. In contrast, MRI provides high-resolution 3D imaging without genetic modifications, providing precise anatomical evaluations. Our study highlights the advantages of MRI over BLI for longitudinal monitoring of orthotopic GBM models. MRI imaging modality opens the possibility to use more clinically relevant patient derived xenograft (PDX) models of GBM in an orthotopic manner, improving the clinical transability to evaluate new GBM treatment modalities.
Citation Format: Mingrui Guo, Ruisong Su, Jeff W H Chor, Zheyan Zhang, Mandy Tan, Xing Qi Teo, Haosheng Feng, Kuan J. Lee, Li Hua, Longyun Zhang, Jie Cai, Guanping Mao, Jingjing Wang, Keefe Chng, Weiping Han, Colin Guo. Magnetic resonance imaging and bioluminescence imaging for evaluating tumor burden in orthotopic glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4179.