In the R21 phase of this proposal we plan to develop new molecularly based imaging technologies for use as noninvasive markers of angiogenic endothelial cells and their death in response to treatment. Polymerized vesicles (PVs) chelated with radionuclide and coated with the monoclonal antibody directed against the alphavbeta3 integrin (antialphavbeta3-AbPVs) will be used as a molecular imaging agent for the detection of newly proliferating angiogenic endothelial cells in both untreated tumors and tumors treated with anti-angiogenic agents. In combination we will also evaluate regional tumor blood flow using the previously validated technique of thallium-201 perfusion imaging. We will determine the time course of tumoral and intratumoral localization of contrast in tumors using 99mTc-anti-alphavbeta3AbPVs and thallium-201 (tumor perfusion) uptake as seen with dual energy micro-SPECT (single photon emission computed tomography) radionuclide imaging. We will also perform immunohistochemistry for specific markers of angiogenesis and apoptosis and correlate these markers with changes in the localization of 99mTc-anti-alphaV beta3 AbPVs and thallium 201. The R33 phase of the program will be to non-invasively detect and quantify neovascularity (angiogenesis) and choose the best imaging regimen for angiogenesis based on these more advanced preclinical studies and develop synthesis and labeling protocols. We plan to perform pharmacokinetics and toxicology studies with preclinical materials and prepare an agent for gamma and SPECT imaging in clinical studies and file an IRB for cancer angiogenesis evaluation.
| Deveau, Michael A; Gutiérrez, Alonso N; Mackie, Thomas R et al. (2010) Dosimetric impact of daily setup variations during treatment of canine nasal tumors using intensity-modulated radiation therapy. Vet Radiol Ultrasound 51:90-6 |
