title: A new optical imaging probe targeting αVβ3 integrin in glioblastoma xenografts.
abstract: α(V)β(3) Integrins are a widely recognized target for in vivo molecular imaging of pathological conditions such as inflammation, cancer and rheumatoid arthritis. We have evaluated the sensitivity of a new, near-infrared fluorescence (NIRF), RGD cyclic probe (DA364) in noninvasive detection of α(V) β(3) integrin-overexpressing tumors. DA364's binding affinity for α(V)β(3) integrin was first evaluated in vitro. Human α(V)β(3) integrin-positive, U-87 MG glioblastoma cells were then xenografted in nude mice, and DA364 was injected intravenously (i.v.) to evaluate its in vivo distribution, specificity and sensitivity in comparison with a commercially available probe. DA364 bound α(V)β(3) integrin on U-87 MG cells with high affinity and specificity, both in vitro and in vivo. This binding specificity was corroborated by the strong inhibition of its tumor uptake induced by nonfluorescent, cyclic-RGD peptides. Ex vivo analysis showed that DA364 accumulated at the tumor site, whereas very low levels were detected in liver and spleen. In conclusion, DA364 allows sensitive and specific detection of transplantable glioblastoma by NIRF imaging, and is thus a promising candidate for the elaboration of imaging and therapeutic probes for α(V)β(3) integrin-overexpressing tumors.
authors.affiliation: Molecular Biotechnology Center, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Lanzardo
authors.forename: Laura
authors.initials: L
authors.lastname: Conti
authors.forename: Chiara
authors.initials: C
authors.lastname: Brioschi
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Bartolomeo
authors.forename: Daniela
authors.initials: D
authors.lastname: Arosio
authors.forename: Laura
authors.initials: L
authors.lastname: Belvisi
authors.forename: Leonardo
authors.initials: L
authors.lastname: Manzoni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Maiocchi
authors.forename: Federico
authors.initials: F
authors.lastname: Maisano
authors.forename: Guido
authors.initials: G
authors.lastname: Forni
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000737:chemistry; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes; D005909:Glioblastoma / Q000175:diagnosis*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000032:analysis*; D051379:Mice; D008819:Mice, Nude; D015336:Molecular Probe Techniques; D009368:Neoplasm Transplantation; D010456:Peptides, Cyclic / Q000737:chemistry; D049268:Positron-Emission Tomography; D019265:Spectroscopy, Near-Infrared; D014018:Tissue Distribution
chemical_list: D002232:Carbocyanines; C571145:DA364; D005456:Fluorescent Dyes; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide