BLUE RIBBON POSTER IMAGING: Oxygen-Enhanced MRI (OE-MRI) In a Heterotopic Syngeneic Murine Model of Non Small Cell Lung Cancer (NSCLC) Treated with Radiation Therapy (RT) and L-Carnosine.
Abstract
Purpose
Hypoxia is a marker of tumours progression and treatment outcomes. This study aims to non-invasively map tumour hypoxia using MR-oximetry in a syngeneic murine model. We evaluate the effect of radiotherapy (RT) and L-carnosine (vascularization modifier) on tumour oxygenation and vascularity.
Methods
C57BL/6 mice (n=14) were implanted subcutaneously with Lewis lung carcinoma cells in the right thigh and assigned into groups as: control (n=3), RT (n=5), and RT with L-carnosine (n=6). Tumour growth was monitored daily using calipers and MRI scans were conducted at a median volume of 0.181 cm3. RT was delivered as a single 8 Gy fraction using a small animal irradiator, 7 days after implantation and 3 days before scanning. Scans included: T2-weighted imaging for anatomical reference, multi-echo gradient echo imaging for effective transverse (R2*) relaxation rate mapping, and T1 saturation recovery for longitudinal (R1) relaxation rate mapping. MR measurements were performed twice, under two gasses: air and oxygen. ΔR1 (R1,O2-R1,air) and ΔR2* (R2*,O2- R2*,air) maps were generated, corresponding to changes in tissue and blood oxygenation, respectively. Baseline R1 and R2* were obtained from the control group. Whole tumour radial segmentation was applied to tumour images. Segments were then used in a linear mixed model to probe the statistical significance of gas breathing and treatment groups. Following imaging, tumours were resected for immunohistochemical analysis.
Results
ΔR1 and ΔR2* were significant under oxygen breathing for each treatment group (p<=0.001). ΔR1 were insignificant for different treatment groups compared to the baseline R1. ΔR2* were significant (p<0.001) under oxygen breathing when comparing both treatment groups’ ΔR2* to control.
Conclusion
R1 is a sensitive marker of oxygen presence but our data did not show a response to radiation or carnosine effects. R2* demonstrates oxygen dependent vascular changes induced by radiation and carnosine with radiation.