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

Geert Hendrikx, Tilman M. Hackeng, Rick van Gorp, Matthias Bauwens, Leon J. Schurgers, Felix M. Mottaghy, Mark J. Post, Ingrid Dijkgraaf*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 In-111-coNGR and In-111-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.

Original languageEnglish
Article number8638549
Number of pages9
JournalContrast Media & Molecular Imaging
Volume2017
DOIs
Publication statusPublished - 2017

Keywords

  • ENDOTHELIAL GROWTH-FACTOR
  • NATIVE CHEMICAL LIGATION
  • CORONARY-ARTERY DISEASE
  • MYOCARDIAL-INFARCTION
  • PET
  • DENDRIMERS
  • ISCHEMIA
  • MOUSE

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