Use of Cyclic Backbone NGR-Based SPECT to Increase Efficacy of Postmyocardial Infarction Angiogenesis Imaging

Contrast Media Mol Imaging. 2017 Oct 24;2017:8638549. doi: 10.1155/2017/8638549. eCollection 2017.

Abstract

As CD13 is selectively expressed in angiogenesis, it can serve as a target for molecular imaging tracers to noninvasively visualize angiogenic processes in vivo. The CD13-targeting moiety NGR was synthesized and cyclized by native chemical ligation (NCL) instead of disulfide bridging, leading to a cyclic peptide backbone: cyclo(Cys-Asn-Gly-Arg-Gly) (coNGR). Beside this new monomeric coNGR, a tetrameric NGR peptide co(NGR)4 was designed and synthesized. After radiolabeling, their in vitro and in vivo characteristics were determined. Both coNGR-based imaging agents displayed considerably higher standardized uptake values (SUVs) at infarcted areas compared to the previously reported disulfide-cyclized cNGR imaging agent. Uptake patterns of 111In-coNGR and 111In-co(NGR)4 coincided with CD13 immunohistochemistry on excised hearts. Blood stability tests indicated better stability for both novel imaging agents after 50 min blood incubation compared to the disulfide-cyclized cNGR imaging agent. In mice, both coNGR peptides cleared rapidly from the blood mainly via the kidneys. In addition, co(NGR)4 showed a significantly higher specific uptake in infarcted myocardium compared to coNGR and thus is a promising sensitive imaging agent for detection of angiogenesis in infarcted myocardium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD13 Antigens / blood
  • Mice
  • Myocardial Infarction / physiopathology*
  • Neovascularization, Pathologic / blood
  • Neovascularization, Pathologic / physiopathology
  • Oligopeptides / chemistry*
  • Tomography, Emission-Computed, Single-Photon / methods*

Substances

  • NGR peptide
  • Oligopeptides
  • CD13 Antigens