title: Enhanced fluorescence diffuse optical tomography with indocyanine green-encapsulating liposomes targeted to receptors for vascular endothelial growth factor in tumor vasculature.
abstract: To develop an indocyanine green (ICG) tracer with slower clearance kinetics, we explored ICG-encapsulating liposomes (Lip) in three different formulations: untargeted (Lip/ICG), targeted to vascular endothelial growth factor (VEGF) receptors (scVEGF-Lip/ICG) by the receptor-binding moiety single-chain VEGF (scVEGF), or decorated with inactivated scVEGF (inactive-Lip/ICG) that does not bind to VEGF receptors. Experiments were conducted with tumor-bearing mice that were placed in a scattering medium with tumors located at imaging depths of either 1.5 or 2.0 cm. Near-infrared fluorescence diffuse optical tomography that provides depth-resolved spatial distributions of fluorescence in tumor was used for the detection of postinjection fluorescent signals. All liposome-based tracers, as well as free ICG, were injected intravenously into mice in the amounts corresponding to 5 nmol of ICG/mouse, and the kinetics of increase and decrease of fluorescent signals in tumors were monitored. A signal from free ICG reached maximum at 15-min postinjection and then rapidly declined with t1/2 of ~20 min. The signals from untargeted Lip/ICG and inactive-Lip/ICG also reached maximum at 15-min postinjection, however, declined somewhat slower than free ICG with t1/2 of ~30 min. By contrast, a signal from targeted scVEGF-Lip/ICG grew slower than that of all other tracers, reaching maximum at 30-min postinjection and declined much slower than that of other tracers with t1/2 of ~90 min, providing a more extended observation window. Higher scVEGF-Lip/ICG tumor accumulation was further confirmed by the analysis of fluorescence on cryosections of tumors that were harvested from animals at 400 min after injection with different tracers.
authors.affiliation: University of Connecticut, Departments of Bioengineering and Electrical and Computer Engineering, Storrs, Connecticut 06269.
authors.forename: Saeid
authors.initials: S
authors.lastname: Zanganeh
authors.affiliation: University of Connecticut, Departments of Bioengineering and Electrical and Computer Engineering, Storrs, Connecticut 06269.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: New York Medical College, Department of Microbiology and Immunology, Valhalla, New York 10595.
authors.forename: Carl V
authors.initials: CV
authors.lastname: Hamby
authors.affiliation: SibTech, Inc., 115A Commerce Drive, Brookfield, Connecticut 06804.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Backer
authors.affiliation: SibTech, Inc., 115A Commerce Drive, Brookfield, Connecticut 06804.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Backer
authors.affiliation: University of Connecticut, Departments of Bioengineering and Electrical and Computer Engineering, Storrs, Connecticut 06269.
authors.forename: Quing
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007208:Indocyanine Green / Q000737:chemistry / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D041622:Tomography, Optical / Q000379:methods*
chemical_list: D005456:Fluorescent Dyes; D008081:Liposomes; D040262:Receptors, Vascular Endothelial Growth Factor; D007208:Indocyanine Green