BLOOD VESSELS IN COLORECTAL TUMOR MODEL--RESPONSE TO ANGIOGENIC THERAPIES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The purpose of this project is to study the development of blood vessels in a colorectal tumor model and the response to anti-angiogenic therapies. Tumors from a human cell line will be implanted on the flank of mice and will be imaged with two different modalities: x-ray and MRI. The x-ray based technique will be digital subtraction angiography (DSA) while the MR-based techniques will be dynamic contrast enhanced (DCE) MRI and angiography. Avastin and Irinitecan are potential drugs that will be utilized in this project. The density, number of vessels, and tortuosity will be studied as a function of tumor size and drug dose. 1) In-vivo MRI (141B Bryan). High resolution MR angiography will be used to study the anatomical distribution of blood vessels in the tumor. DCE-MRI will complement the anatomical measurements with functional information by quantifying the transfer rate of contrast from intravascular to extravascular space which is a measure of vessel leakiness. A custom build surface coil will be used for signal reception. The contrast agents employed in these scans will be Magnevist and blood-pool liposomal gadolinium. Imaging time for MR scans will be approximately 45 minutes. 2) In-vivo X-ray (131 Bryan). DSA imaging provides fast acquisition options not easily achieved with MR that enables the study of contrast uptake and/or clearance at heartbeat resolution. Arterial supply can be distinguished from venous pathways through the analysis of time density curves (TDC). TDCs are also used to measure the mean transit time, blood flow, and blood volume in a region of interest. Isovue250 will be injected in the tail vein and/or femoral artery (or carotid artery if the tumors are implanted in the neck). Imaging time for DSA scans will be approximately 20 minutes. 3) At the completion of the imaging studies, animals will be sacrificed by anesthetic overdose and tumors will be excised and fixed in formalin or Bouin's for conventional histology.