title: (99m)Tc-Galacto-RGD2: a novel 99mTc-labeled cyclic RGD peptide dimer useful for tumor imaging.
abstract: This study sought to evaluate [(99m)Tc(HYNIC-Galacto-RGD2)(tricine)(TPPTS)] ((99m)Tc-Galacto-RGD2: HYNIC = 6-hydrazinonicotinyl; Galacto-RGD2 = Glu[cyclo[Arg-Gly-Asp-D-Phe-Lys(SAA-PEG2-(1,2,3-triazole)-1-yl-4-methylamide)]]2 (SAA = 7-amino-L-glycero-L-galacto-2,6-anhydro-7-deoxyheptanamide, and PEG2 = 3,6-dioxaoctanoic acid); and TPPTS = trisodium triphenylphosphine-3,3',3″-trisulfonate) as a new radiotracer for tumor imaging. Galacto-RGD2 was prepared via the copper(I)-catalyzed 1,3-dipolar azide-alkyne Huisgen cycloaddition. HYNIC-Galacto-RGD2 was prepared by reacting Galacto-RGD2 with sodium succinimidyl 6-(2-(2-sulfonatobenzaldehyde)hydrazono)nicotinate (HYNIC-OSu) in the presence of diisopropylethylamine, and was evaluated for its integrin αvβ3 binding affinity against (125)I-echistatin bound to U87MG glioma cells. The IC50 value for HYNIC-Galacto-RGD2 was determined to be 20 ± 2 nM. (99m)Tc-Galacto-RGD2 was prepared in high specific activity (∼ 185 GBq/μmol) and high radiochemical purity (>95%), and was evaluated in athymic nude mice bearing U87MG glioma xenografts for its tumor-targeting capability and biodistribution. The tumor uptake of (99m)Tc-Galacto-RGD2 was 10.30 ± 1.67, 8.37 ± 2.13, 6.86 ± 1.33, and 5.61 ± 1.52%ID/g at 5, 30, 60, and 120 min p.i., respectively, which was in agreement with high integrin αvβ3 expression on glioma cells and neovasculature. Its lower uptake in intestines, lungs, and spleen suggests that (99m)Tc-Galacto-RGD2 has advantages over (99m)Tc-3P-RGD2 ([(99m)Tc(HYNIC-3P-RGD2)(tricine)(TPPTS)]: 3P-RGD2 = PEG4-E[PEG4-c(RGDfK)]2; PEG4 = 15-amino-4,7,10,13-tetraoxapentadecanoic acid) for imaging tumors in the chest and abdominal regions. U87MG tumors were readily detected by SPECT and the tumor uptake of (99m)Tc-Galacto-RGD2 was integrin αvβ3-specific. (99m)Tc-Galacto-RGD2 also had very high metabolic stability. On the basis of results from this study, it was concluded that (99m)Tc-Galacto-RGD2 is an excellent radiotracer for imaging integrin αvβ3-positive tumors and related metastases.
authors.affiliation: School of Health Sciences, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Shundong
authors.initials: S
authors.lastname: Ji
authors.forename: Andrzej
authors.initials: A
authors.lastname: Czerwinski
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Shao
authors.forename: Francisco
authors.initials: F
authors.lastname: Valenzuela
authors.forename: Paweł
authors.initials: P
authors.lastname: Sowiński
authors.forename: Satendra
authors.initials: S
authors.lastname: Chauhan
authors.forename: Michael
authors.initials: M
authors.lastname: Pennington
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005910:Glioma / Q000175:diagnosis; D006020:Glycopeptides / Q000737:chemistry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000737:chemistry*; D015609:Organotechnetium Compounds; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D006020:Glycopeptides; D009842:Oligopeptides; D015609:Organotechnetium Compounds; C047981:arginyl-glycyl-aspartic acid