title: Molecular imaging of tumor angiogenesis using alphavbeta3-integrin targeted multimodal quantum dots.
abstract: Molecular imaging of angiogenesis is urgently needed for diagnostic purposes such as early detection, monitoring of (angiostatic) therapy and individualized therapy. Multimodality molecular imaging is a promising and refined technique to study tumor angiogenesis, which has so far been largely unexplored due to the lack of suitable multimodal contrast agents. Here, we report on the application of a novel alphavbeta3-specific quantum dot-based nanoparticle, which has been optimized for both optical and magnetic resonance detection of tumor angiogenesis. Upon intravenous injection of RGD-pQDs in tumor-bearing mice, intravital microscopy allowed the detection of angiogenically activated endothelium at cellular resolution with a small scanning window and limited penetration depth, while magnetic resonance imaging was used to visualize angiogenesis at anatomical resolution throughout the entire tumor. Fluorescence imaging allowed whole-body investigation of angiogenic activity. Using these quantum dots and the aforementioned imaging modalities, the angiogenic tumor vasculature was readily detected with the highest angiogenic activity occurring in the periphery of the tumor. This nanoparticle may be employed for multimodality imaging of a variety of diseases that are accompanied by activation of endothelial cells. Furthermore, the current technology might be developed for molecular imaging of other pathophysiological processes.
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. willem.mulder@mountsinai.org
authors.forename: Willem J M
authors.initials: WJ
authors.lastname: Mulder
authors.forename: Karolien
authors.initials: K
authors.lastname: Castermans
authors.forename: Judy R
authors.initials: JR
authors.lastname: van Beijnum
authors.forename: Mirjam G A
authors.initials: MG
authors.lastname: Oude Egbrink
authors.forename: Patrick T K
authors.initials: PT
authors.lastname: Chin
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.forename: Clemens W G M
authors.initials: CW
authors.lastname: Löwik
authors.forename: Eric L
authors.initials: EL
authors.lastname: Kaijzel
authors.forename: Ivo
authors.initials: I
authors.lastname: Que
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Strijkers
authors.forename: Arjan W
authors.initials: AW
authors.lastname: Griffioen
authors.forename: Klaas
authors.initials: K
authors.lastname: Nicolay
mesh_terms: D000818:Animals; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000098:blood supply; D003952:Diagnostic Imaging; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D045663:Quantum Dots
chemical_list: D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid