Imaging integrin AvB3 expression during tumor growth
Abstract
Integrin αvβ3 plays a pivotal role in tumor angiogenesis. Over the last decade, many radiolabeled cyclic RGD peptides have been evaluated as αvβ3-targeted radiotracers. Despite significant progress in this area, there is a continuing need for more efficient radiotracers with high tumor uptake and tumor-to-background ratios, which are important for early cancer detection. This project focuses on the biological evaluation of [99mTc(HYNIC-K(NIC)-3P 4-RGD2)(tricine)] (99mTc-K(NIC)-3P-RGD2) as a novel SPECT radiotracer. Biodistribution and imaging studies were performed on athymic nude mice bearing U87MG, MDA-MB-435, A549 or PC3 tumor xenografts. Immunohistochemistry staining was performed using the xenografted tumor tissues to determine their β3 expression levels. It is found that the radiotracer tumor uptake followed the trend: U87MG > MDA-MB-435 ∼ A549 > PC3. The total β3 expression levels follow the general trend: U87MG > MDA-MB-435 ∼ A549 > PC3. There is a linear relationship between the radiotracer %ID/g tumor uptake and the total β3 expression levels. The radiotracer tumor uptake is contributed by the αvβ 3 expressed on both tumor cells and activated endothelial cells of the tumor neovasculature. 99mTc-K(NIC)-3P-RGD2 is able to monitor the tumor αvβ3 expression in a noninvasive fashion.
Degree
M.S.
Advisors
Liu, Purdue University.
Subject Area
Pharmacy sciences|Medical imaging
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