Quantitative molecular magnetic resonance imaging of tumor angiogenesis using cNGR-labeled paramagnetic quantum dots.
The objective of this study was to develop and apply cyclic Asn-Gly-Arg (cNGR)-labeled paramagnetic quantum dots (cNGR-pQDs) for the noninvasive assessment of tumor angiogenic activity using quantitative in vivo molecular magnetic resonance imaging (MRI). cNGR was previously shown to colocalize with CD13, an aminopeptidase that is highly overexpressed on angiogenic tumor endothelium. Because angiogenesis is important for tumor growth and metastatization, its in vivo detection and quantification may allow objective diagnosis of tumor status and evaluation of treatment response. I.v. injection of cNGR-pQDs in tumor-bearing mice resulted in increased quantitative contrast, comprising increased longitudinal relaxation rate and decreased proton visibility, in the tumor rim but not in tumor core or muscle tissue. This showed that cNGR-pQDs allow in vivo quantification and accurate localization of angiogenic activity. MRI results were validated using ex vivo two-photon laser scanning microscopy (TPLSM), which showed that cNGR-pQDs were primarily located on the surface of tumor endothelial cells and to a lesser extent in the vessel lumen. In contrast, unlabeled pQDs were not or only sparsely detected with both MRI and TPLSM, supporting a high specificity of cNGR-pQDs for angiogenic tumor vasculature.
Oostendorp
Marlies
M
Department of Radiology, Maastricht University Hospital, the Netherlands.
Douma
Kim
K
Hackeng
Tilman M
TM
Dirksen
Anouk
A
Post
Mark J
MJ
van Zandvoort
Marc A M J
MA
Backes
Walter H
WH
D000230:Adenocarcinoma / Q000098:blood supply*; D000465:Algorithms; D000818:Animals; D001667:Binding, Competitive; D015179:Colorectal Neoplasms / Q000098:blood supply*; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry* / Q000493:pharmacokinetics; D045663:Quantum Dots; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D003287:Contrast Media; C526428:NGR peptide; D009842:Oligopeptides