title: A novel Tc-99m and fluorescence labeled peptide as a multimodal imaging agent for targeting angiogenesis in a murine hindlimb ischemia model.
abstract: The serine-aspartic acid-valine (SDV) peptide binds specifically to integrin αvβ3. We developed a Tc-99m and TAMRA labeled peptide, Tc-99m SDV-ECG-K-TAMRA for multimodal imaging of angiogenesis. Tc-99m SDV-ECG-K-TAMRA was prepared in high yield (>96%) and showed low cytotoxicity. Tc-99m tetrofosmin images 1 week after operation, revealed significantly decreased perfusion of the ischemic hindlimb, and the perfusion recovered gradually for 4 weeks. In contrast, Tc-99m SDV-ECG-K-TAMRA uptake was maximal 1 week after the operation (ischemic-to-non-ischemic uptake ratio =5.03±1.01) and decreased gradually. The ischemic-to-non-ischemic ratio of Tc-99m SDV-ECG-K-TAMRA and Tc-99m tetrofosmin was strongly negatively correlated (r =-0.94). A postmortem analysis revealed increased angiogenesis markers and uptake of Tc-99m SDV-ECG-K-TAMRA by ischemic tissue. Our in vivo and in vitro studies revealed substantial uptake of Tc-99m SDV-ECG-K-TAMRA by ischemic tissue. Tc-99m SDV-ECG-K-TAMRA could be a good candidate dual-modality imaging agent to assess angiogenesis.
authors.affiliation: Department of Nuclear Medicine and Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, Iksan, Jeollabuk-do, Korea.
authors.forename: Myoung
authors.initials: M
authors.lastname: Hyoun 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.
authors.forename: Chang
authors.initials: C
authors.lastname: Guhn 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. Electronic address: akaxan@nate.com.
authors.forename: Dae-Weung
authors.initials: DW
authors.lastname: Kim
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000000981:diagnostic imaging* / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D064847:Multimodal Imaging / Q000379:methods; D018919:Neovascularization, Physiologic; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D012235:Rhodamines / Q000737:chemistry / Q000493:pharmacokinetics; D013667:Technetium / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: C114557:5-carboxytetramethylrhodamine succinimidyl ester; D005456:Fluorescent Dyes; D009842:Oligopeptides; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D012235:Rhodamines; C078700:technetium tc-99m tetrofosmin; D013667:Technetium
keywords: Angiogenesis; Multimodal imaging; Serine-aspartic acid-valine; TAMRA; Tc-99m