title: Tumor angiogenesis phenotyping by nanoparticle-facilitated magnetic resonance and near-infrared fluorescence molecular imaging.
abstract: One of the challenges of tailored antiangiogenic therapy is the ability to adequately monitor the angiogenic activity of a malignancy in response to treatment. The α(v)β(3) integrin, highly overexpressed on newly formed tumor vessels, has been successfully used as a target for Arg-Gly-Asp (RGD)-functionalized nanoparticle contrast agents. In the present study, an RGD-functionalized nanocarrier was used to image ongoing angiogenesis in two different xenograft tumor models with varying intensities of angiogenesis (LS174T > EW7). To that end, iron oxide nanocrystals were included in the core of the nanoparticles to provide contrast for T(2)*-weighted magnetic resonance imaging (MRI), whereas the fluorophore Cy7 was attached to the surface to enable near-infrared fluorescence (NIRF) imaging. The mouse tumor models were used to test the potential of the nanoparticle probe in combination with dual modality imaging for in vivo detection of tumor angiogenesis. Pre-contrast and post-contrast images (4 hours) were acquired at a 9.4-T MRI system and revealed significant differences in the nanoparticle accumulation patterns between the two tumor models. In the case of the highly vascularized LS174T tumors, the accumulation was more confined to the periphery of the tumors, where angiogenesis is predominantly occurring. NIRF imaging revealed significant differences in accumulation kinetics between the models. In conclusion, this technology can serve as an in vivo biomarker for antiangiogenesis treatment and angiogenesis phenotyping.
authors.affiliation: Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Jarzyna
authors.forename: Lisette H
authors.initials: LH
authors.lastname: Deddens
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Kann
authors.forename: Sarayu
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Claudia
authors.initials: C
authors.lastname: Calcagno
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Anita
authors.initials: A
authors.lastname: Gianella
authors.forename: Rick M
authors.initials: RM
authors.lastname: Dijkhuizen
authors.forename: Arjan W
authors.initials: AW
authors.lastname: Griffioen
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.forename: Willem J M
authors.initials: WJ
authors.lastname: Mulder
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000378:metabolism; D003287:Contrast Media; D004195:Disease Models, Animal; D005453:Fluorescence; D006801:Humans; D007124:Immunoenzyme Techniques; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D057054:Molecular Imaging; D053758:Nanoparticles; D009389:Neovascularization, Pathologic; D009842:Oligopeptides / Q000037:antagonists & inhibitors; D012512:Sarcoma, Ewing / Q000098:blood supply / Q000175:diagnosis* / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared
chemical_list: D003287:Contrast Media; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid