title: 111In- and IRDye800CW-Labeled PLA-PEG Nanoparticle for Imaging Prostate-Specific Membrane Antigen-Expressing Tissues.
abstract: Targeted delivery of drug-encapsulated nanoparticles is a promising new approach to safe and effective therapeutics for cancer. Here we investigate the pharmacokinetics and biodistribution of a prostate-specific membrane antigen (PSMA)-targeted nanoparticle based on a poly(lactic acid)-polyethylene glycol copolymer by utilizing single photon emission computed tomography (SPECT) and fluorescence imaging of a low-molecular-weight, PSMA-targeting moiety attached to the surface and oriented toward the outside environment. Tissue biodistribution of the radioactive, PSMA-targeted nanoparticles in mice containing PSMA(+) PC3 PIP and PSMA(-) PC3 flu (control) tumors demonstrated similar accumulation compared to the untargeted particles within all tissues except for the tumor and liver by 96 h postinjection. For PSMA(+) PC3 PIP tumor, the targeted nanoparticle demonstrated retention of 6.58% injected dose (ID)/g at 48 h and remained nearly at that level out to 96 h, whereas the untargeted nanoparticle showed a 48 h retention of 8.17% ID/g followed by a significant clearance to 2.37% ID/g at 96 h (P < 0.02). On the other hand, for control tumor, both targeted and untargeted particles displayed similar 48 h retentions and rates of clearance over 96 h. Ex vivo microscopic analysis with near-infrared versions of the nanoparticles indicated retention within PSMA(+) tumor epithelial cells as well as tumor-associated macrophages for targeted particles and primarily macrophage-associated uptake for the untargeted particles. Retention in control tumor was primarily associated with tumor vasculature and macrophages. The data demonstrate the utility of radioimaging to assess nanoparticle biodistribution and suggest that active targeting has a modest positive effect on tumor localization of PSMA-targeted PLA-PEG nanoparticles that have been derivatized for imaging.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Sangeeta R
authors.initials: SR
authors.lastname: Banerjee
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Foss
authors.affiliation: BIND Therapeutics, Cambridge, Massachusetts 02139, United States.
authors.forename: Allen
authors.initials: A
authors.lastname: Horhota
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Mrudula
authors.initials: M
authors.lastname: Pullambhatla
authors.affiliation: BIND Therapeutics, Cambridge, Massachusetts 02139, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: McDonnell
authors.affiliation: BIND Therapeutics, Cambridge, Massachusetts 02139, United States.
authors.forename: Stephen
authors.initials: S
authors.lastname: Zale
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Martin G
authors.identifier: 0000-0001-6753-3010
authors.initials: MG
authors.lastname: Pomper
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D001557:Benzenesulfonates / Q000493:pharmacokinetics*; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D007211:Indoles / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D019265:Spectroscopy, Near-Infrared; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D000954:Antigens, Surface; D001557:Benzenesulfonates; D005456:Fluorescent Dyes; C562366:IRDye 800CW; D007205:Indium Radioisotopes; D007211:Indoles; D011108:Polymers; D019275:Radiopharmaceuticals; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II