99mTc-Galacto-RGD2: A Novel 99mTc-Labeled Cyclic RGD Peptide Dimer Useful for Tumor Imaging

• DOI: 10.1021/mp400085d
• Publication Date: 2013-07-22T14:04:08Z
• Authors: Shundong Ji; Andrzej Czerwinski; Yang Zhou; Guoqiang Shao; Francisco Valenzuela; Paweł Sowiński; Satendra Chauhan; Michael Pennington; Shuang Liu
• Keywords: Biodistribution

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); TPPTS trisodium triphenylphosphine-3,3',3″-trisulfonate) as a new radiotracer for tumor imaging. was prepared via the copper(I)-catalyzed 1,3-dipolar azide-alkyne Huisgen cycloaddition. HYNIC-Galacto-RGD2 by reacting with sodium succinimidyl 6-(2-(2-sulfonatobenzaldehyde)hydrazono)nicotinate (HYNIC-OSu) in presence of diisopropylethylamine, evaluated its integrin αvβ3 binding affinity against (125)I-echistatin bound U87MG glioma cells. The IC50 value determined be 20 ± 2 nM. (99m)Tc-Galacto-RGD2 high specific activity (∼ 185 GBq/μmol) radiochemical purity (>95%), athymic nude mice bearing xenografts tumor-targeting capability biodistribution. uptake 10.30 1.67, 8.37 2.13, 6.86 1.33, 5.61 1.52%ID/g at 5, 30, 60, 120 min p.i., respectively, which agreement expression on cells neovasculature. Its lower intestines, lungs, spleen suggests that 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) imaging tumors chest abdominal regions. were readily detected SPECT αvβ3-specific. also had very metabolic stability. On basis results from this study, it concluded is an excellent αvβ3-positive related metastases.