The goal of this proposal is to assess whether a change in blood flow in response to a vasoactive agent can be used to predict changes in tumor response to radiation following the administration of the agent. The results will have profound implications if one could determine before therapy which tumors will respond to vasoactive modification of radiation treatment. A promising NMR perfusion imaging (NMR-PI) technique will be used to measure changes in tumor perfusion distribution in response to nicotinamide and mild heat 41 degrees C for 1 hour) in models of human tumors.
The specific aims of the proposal are: 1) To obtain NMR perfusion images before and after the administration of nicotinamide in several tumor models that are expected to span the range of vascular responses to nicotinamide. 2) To extend NMR-PI measurements before and after the administration of mild heat with and without nicotinamide. 3) To obtain NMR perfusion images in spontaneous tumors before and after the administration of nicotinamide or nicotinamide/mild heat. Tumors arising from genetically engineered, transgenic mice will be used in this study. 4) To determine whether NMR-PI mean values in the tumor models employed compare favorably with measurements of tumor blood flow in the same model systems using more widely-accepted methods. NMR perfusion measurements in rat and mouse tumor models will be compared with the average value from radioactive microspheres and rubidium uptake, respectively. 5) To determine the modification in tumor radiation response following the administration of nicotinamide/mild heat in spontaneous tumor models. And to determine in the same animals the change in a blood flow parameter due to the administration of nicotinamide/mild heat.
| Brown, S L; Ewing, J R; Kolozsvary, A et al. (1999) Magnetic resonance imaging of perfusion in rat cerebral 9L tumor after nicotinamide administration. Int J Radiat Oncol Biol Phys 43:627-33 |
| Lew, Y S; Brown, S L; Griffin, R J et al. (1999) Arsenic trioxide causes selective necrosis in solid murine tumors by vascular shutdown. Cancer Res 59:6033-7 |
