title: Imaging of Vx-2 rabbit tumors with alpha(nu)beta3-integrin-targeted 111In nanoparticles.
abstract: Earlier tumor detection can improve 5-year survival of patients, particularly among those presenting with cancers less than 1 cm in diameter. alpha(nu)beta(3)-Targeted (111)In nanoparticles (NP) were developed and studied for detection of tumor angiogenesis. Studies were conducted in New Zealand white rabbits implanted 12 days earlier with Vx-2 tumor. alpha(nu)beta(3)-Targeted (111)In/NP bearing approximately 10 (111)In/NP vs. approximately 1 (111)In/NP nuclide payloads were compared to nontargeted radiolabeled control particles. In vivo competitive binding studies were used to assess ligand-targeting specificity. alpha(nu)beta(3)-Integrin-targeted NP with approximately 10 (111)In/NP provided better (p < 0.05) tumor-to-muscle ratio contrast (6.3 +/- 0.2) than approximately 1 (111)In/NP (5.1 +/- 0.1) or nontargeted particles with approximately 10 (111)In/NP (3.7 +/- 0.1) over the initial 2-hr postinjection. At 18 hr, mean tumor activity in rabbits receiving alpha(nu)beta(3)-integrin-targeted NP was 4-fold higher than the nontargeted control. Specificity of the NP for the tumor neovasculature was supported by in vivo competition studies and by fluorescence microscopy of alpha(nu)beta(3)-targeted fluorescent-labeled NP. Biodistribution studies revealed that the primary clearance organ in rabbits as a %ID/g tissue was the spleen. Circulatory half-life (t(1/2)beta) was estimated to be approximately 5 hr using a 2-compartment model. alpha(nu)beta(3)-Targeted (111)In perfluorocarbon NP may provide a clinically useful tool for sensitively detecting angiogenesis in nascent tumors, particularly in combination with secondary high-resolution imaging modalities, such as MRI.
authors.affiliation: Department of Medicine, Division of Cardiology, Washington University Medical School, St. Louis, MO, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Hu
authors.forename: Michal
authors.initials: M
authors.lastname: Lijowski
authors.forename: Huiying
authors.initials: H
authors.lastname: Zhang
authors.forename: Kathryn C
authors.initials: KC
authors.lastname: Partlow
authors.forename: Shelton D
authors.initials: SD
authors.lastname: Caruthers
authors.forename: Garry
authors.initials: G
authors.lastname: Kiefer
authors.forename: Gyongyi
authors.initials: G
authors.lastname: Gulyas
authors.forename: Phillip
authors.initials: P
authors.lastname: Athey
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Scott
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Wickline
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lanza
mesh_terms: D000818:Animals; D007205:Indium Radioisotopes; D039302:Integrin alphaVbeta3 / Q000032:analysis*; D008279:Magnetic Resonance Imaging; D008297:Male; D053758:Nanoparticles; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000000981:diagnostic imaging; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D011817:Rabbits; D011877:Radionuclide Imaging
chemical_list: D007205:Indium Radioisotopes; D039302:Integrin alphaVbeta3