title: 99mTc-labeled cyclic RGD peptides for noninvasive monitoring of tumor integrin αVβ3 expression.
abstract: 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.
authors.affiliation: School of Health Sciences, Purdue University, West Lafayette, IN, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Young-Seung
authors.initials: YS
authors.lastname: Kim
authors.forename: Sudipta
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Jiyun
authors.initials: J
authors.lastname: Shi
authors.forename: Haijuan
authors.initials: H
authors.lastname: Gao
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000096:biosynthesis*; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000493:pharmacokinetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051598:Whole Body Imaging; D023041:Xenograft Model Antitumor Assays
chemical_list: D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C561921:technetium 99m (HYNIC-3PRGD(2))(tricine)(TPPTS); C047981:arginyl-glycyl-aspartic acid