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

Abstract EN

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.