This report describes the
biologic evaluations of [99mTc(HYNIC-3P-RGD2)(
tricine)(TPPTS)] (99mTc-3P-RGD2: 6-hydrazinonicotinyl; 3P-RGD2 = PEG4-E[PEG4-c(RGDfK)]2; PEG4 = 15-amino-4,7,10,13-tetraoxapentadecanoic
acid; and TPPTS = trisodium
triphenylphosphine-3,3',3''-trisulfonate), [99mTc(HYNIC-3G-RGD2)(
tricine)(TPPTS)] (99mTc-3G-RGD2: 3G-RGD2 = G3-E[G3-c(RGDfK)]2 and G3 =
Gly-Gly-Gly), and 99mTcO(MAG2-3G-RGD2) (MAG2 = mercaptoacetylglycylglycyl) as radiotracers for noninvasive imaging of
tumor integrin αvβ3 expression in five xenografted
tumor-bearing models. Biodistribution and imaging studies were performed in athymic nude mice bearing U87MG, MDA-MB-435, A549, HT29, or PC-3
tumor xenografts. Immunochemistry was performed using the cultured primary
tumor cells and xenografted
tumor tissues. It was found that the radiotracer
tumor uptake followed the trend U87MG > MDA-MB-435 ≈ HT29 ≈ A549 > PC-3. The total
integrin β3 expression levels followed the general trend: U87MG > MDA-MB-435 ≈ A549∼HT29 > PC-3. There is a linear relationship between the radiotracer injected dose per gram
tumor uptake and the total
integrin β3 expression levels. On the basis of these, it was concluded that radiotracer
tumor uptake is contributed by
integrin αvβ3 expressed on
tumor cells and activated endothelial cells of the
tumor neovasculature.
99mTc-3P-RGD2 has the capability to monitor
integrin αvβ3 expression in a noninvasive fashion.