title: MR angiogenesis imaging with Robo4- vs. alphaVbeta3-targeted nanoparticles in a B16/F10 mouse melanoma model.
abstract: The primary objective of this study was to utilize MR molecular imaging to compare the 3-dimensional spatial distribution of Robo4 and α(V)β(3)-integrin as biosignatures of angiogenesis, in a rapidly growing, syngeneic tumor. B16-F10 melanoma-bearing mice were imaged with magnetic resonance (MR; 3.0 T) 11 d postimplantation before and after intravenous administration of either Robo4- or α(V)β(3)-targeted paramagnetic nanoparticles. The percentage of MR signal-enhanced voxels throughout the tumor volume was low and increased in animals receiving α(V)β(3)- and Robo4-targeted nanoparticles. Neovascular signal enhancement was predominantly associated with the tumor periphery (i.e., outer 50% of volume). Microscopic examination of tumors coexposed to the Robo4- and α(V)β(3)-targeted nanoparticles corroborated the MR angiogenesis mapping results and further revealed that Robo4 expression generally colocalized with α(V)β(3)-integrin. Robo4- and α(V)β(3)-targeted nanoparticles were compared to irrelevant or nontargeted control groups in all modalities. These results suggest that α(V)β(3)-integrin and Robo4 are useful biomarkers for noninvasive MR molecular imaging in syngeneic mouse tumors, but α(V)β(3)-integrin expression was more detectable by MR at 3.0 T than Robo4. Noninvasive, neovascular assessments of the MR signal of Robo4, particularly combined with α(V)β(3)-integrin expression, may help define tumor character prior to and following cancer therapy.
authors.affiliation: Washington University Medical School, St. Louis, MO 63108, USA.
authors.forename: Kent S
authors.initials: KS
authors.lastname: Boles
authors.forename: Anne H
authors.initials: AH
authors.lastname: Schmieder
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Koch
authors.forename: Richard A D
authors.initials: RA
authors.lastname: Carano
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Shelton D
authors.initials: SD
authors.lastname: Caruthers
authors.forename: Raymond K
authors.initials: RK
authors.lastname: Tong
authors.forename: Scott
authors.initials: S
authors.lastname: Stawicki
authors.forename: Grace
authors.initials: G
authors.lastname: Hu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Scott
authors.forename: Huiying
authors.initials: H
authors.lastname: Zhang
authors.forename: Benton A
authors.initials: BA
authors.lastname: Reynolds
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Wickline
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lanza
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D004195:Disease Models, Animal; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008545:Melanoma / Q000175:diagnosis*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D057054:Molecular Imaging / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000378:metabolism*; D013194:Staining and Labeling
chemical_list: D015415:Biomarkers; D039302:Integrin alphaVbeta3; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C540792:Robo4 protein, mouse