Purpose: The purpose of this study is to monitor in vivo the IR dose dependent response of NF-κB and tumor
hemodynamics as a function of time.
Material and Methods: An MDA-231 breast cancer cell line was stably transfected with a firefly luciferase gene
within the NF-kappaB promoter. Tumors on the right flank irradiated with a single fractionated dose of 5Gy or 10Gy.
Over two weeks, photoacoustic spectroscopy (PCT-S), bioluminescence imaging (BLI), and dynamic contrast
enhanced CT (DCE-CT) was used to monitor hemoglobin status, NF-kappaB expression, and physiology, respectively.
Results: From the BLI, an increase in NF-kappaB expression was observed in both the right (irradiation) and left (nonirradiated)
tumors, which peaked at 8-12 hours, returned to basal levels after 24 hours, and increased a second time
from 3 to 7 days. This data identifies both a radiation-induced bystander effect and a bimodal longitudinal response
associated with NF-κB-controlled luciferase promoter. The physiological results from DCE-CT measured an increase
in perfusion (26%) two days after radiation and both a decrease in perfusion and an increase in fp by week 1 (10Gy
cohort). PCT-S measured increased levels of oxygen saturation two days post IR, which did not change after 1 week.
Initially, NF-κB would modify hemodynamics to increase oxygen delivery after IR insult. The secondary response
appears to modulate tumor angiogenesis.
Conclusions: A bimodal response to radiation was detected with NF-kappaB-controlled luciferase reporter with a
concomitant hemodynamic response associated with tumor hypoxia. Experiments are being performed to increase