title: A novel Tc-99 m and fluorescence labeled peptide as a multimodal imaging agent for targeting angiogenesis in a murine tumor model.
abstract: The serine-aspartic acid-valine (SDV) peptide binds specifically to integrin αVβ3. In the present study, we successfully developed a TAMRA-GHEG-ECG-SDV peptide labeled with both Tc-99 m and TAMRA to target the integrin αVβ3of tumor cells; furthermore, we evaluated the diagnostic performance of Tc-99 m TAMRA-GHEG-ECG-SDV as a dual-modality imaging agent for tumor of the murine model. TAMRA-GHEG-ECG-SDV was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-SDV with Tc-99 m was done using ligand exchange methods. Labeling stability and cytotoxicity studies were performed. Gamma camera imaging, biodistribution and ex vivo imaging studies were performed in murine models with HT-1080 and HT-29 tumors. A tumor tissue slide was prepared and analyzed using confocal microscopy. After radiolabeling procedures with Tc-99 m, the Tc-99 m TAMRA-GHEG-ECG-SDV complexes were prepared in high yield (>99%). In the gamma camera imaging study, a substantial uptake of Tc-99 m TAMRA-GHEG-ECG-SDV into HT-1080 tumor (integrin αVβ3positive) and low uptake of Tc-99 m TAMRA-GHEG-ECG-SDV into HT-29 tumor (integrin αVβ3negative) were demonstrated. A competition study revealed that HT-1080 tumor uptake was effectively blocked by the co-injection of an excess concentration of SDV. Specific uptake of Tc-99 m TAMRA-GHEG-ECG-SDV was confirmed by biodistribution, ex vivo imaging and confocal microscopy studies. Our in vivo and in vitro studies revealed substantial uptake of Tc-99 m TAMRA-GHEG-ECG-SDV in the integrin αVβ3-positive tumor. Tc-99 m TAMRA-GHEG-ECG-SDV could be a good candidate for a dual-modality imaging agent targeting tumor angiogenesis. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Nuclear Medicine and Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, Iksan, Jeollabuk-do, Korea.
authors.forename: Myoung Hyoun
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine and Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, Iksan, Jeollabuk-do, Korea.
authors.forename: Chang Guhn
authors.initials: CG
authors.lastname: Kim
authors.affiliation: Research Unit of Molecular Imaging Agent (RUMIA), Wonkwang University School of Medicine, Iksan, Jeollabuk-do, Korea.
authors.forename: Seul-Gi
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine and Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, Iksan, Jeollabuk-do, Korea.|Research Unit of Molecular Imaging Agent (RUMIA), Wonkwang University School of Medicine, Iksan, Jeollabuk-do, Korea.
authors.forename: Dae-Weung
authors.initials: DW
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D019073:HT29 Cells; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D064847:Multimodal Imaging / Q000379:methods*; D009369:Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000000981:diagnostic imaging; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D010455:Peptides / Q000737:chemistry*; D012235:Rhodamines / Q000737:chemistry; D013667:Technetium
chemical_list: C114557:5-carboxytetramethylrhodamine succinimidyl ester; D003287:Contrast Media; D039302:Integrin alphaVbeta3; D010455:Peptides; D012235:Rhodamines; D013667:Technetium
keywords: SDV; TAMRA; Tc-99 m; angiogenesis; multimodal imaging; serine-aspartic acid-valine