Author/Authors :
Hendrikx, Geert Department of Radiology and Nuclear Medicine - Cardiovascular Research Institute Maastricht (CARIM) - Maastricht University Medical Center (MUMC+) - Maastricht, Netherlands , Hackeng, Tilman M Department of Biochemistry - Cardiovascular Research Institute Maastricht (CARIM) - Maastricht University Medical Center (MUMC+) - Maastricht, Netherlands , Gorp, Rick van Department of Biochemistry - Cardiovascular Research Institute Maastricht (CARIM) - Maastricht University Medical Center (MUMC+) - Maastricht, Netherlands , Bauwens, Matthias Department of Radiology and Nuclear Medicine - Cardiovascular Research Institute Maastricht (CARIM) - Maastricht University Medical Center (MUMC+) - Maastricht, Netherlands , Schurgers, Leon J. Department of Biochemistry - Cardiovascular Research Institute Maastricht (CARIM) - Maastricht University Medical Center (MUMC+) - Maastricht, Netherlands , Mottaghy, Felix M Department of Radiology and Nuclear Medicine - Cardiovascular Research Institute Maastricht (CARIM) - Maastricht University Medical Center (MUMC+) - Maastricht, Netherlands , Post, Mark J Department of Physiology - Cardiovascular Research Institute Maastricht (CARIM) - Maastricht University Medical Center (MUMC+) - Maastricht, Netherlands , Dijkgraaf, Ingrid Department of Biochemistry - Cardiovascular Research Institute Maastricht (CARIM) - Maastricht University Medical Center (MUMC+) - Maastricht, Netherlands
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.
Keywords :
SPECT , NGR , Postmyocardial , Angiogenesis
