title: Biodistribution and fate of core-labeled125I polymeric nanocarriers prepared by Flash NanoPrecipitation (FNP).
abstract: Non-invasive medical imaging techniques such as positron emission tomography (PET) imaging are powerful platforms to track the fate of radiolabeled materials for diagnostic or drug delivery applications. Polymer-based nanocarriers tagged with non-standard PET radionuclides with relatively long half-lives (e.g.64Cu: t1/2= 12.7 h,76Br: t1/2= 16.2h,89Zr: t1/2= 3.3 d,124I: t1/2= 4.2 d) may greatly expand applications of nanomedicines in molecular imaging and therapy. However, radiolabeling strategies that ensure stablein vivoassociation of the radiolabel with the nanocarrier remain a significant challenge. In this study, we covalently attach radioiodine to the core of pre-fabricated nanocarriers. First, we encapsulated polyvinyl phenol within a poly(ethylene glycol) coating using Flash NanoPrecipitation (FNP) to produce stable 75 nm and 120 nm nanocarriers. Following FNP, we radiolabeled the encapsulated polyvinyl phenol with125I via electrophilic aromatic substitution in high radiochemical yields (> 90%). Biodistribution studies reveal low radioactivity in the thyroid, indicating minimal leaching of the radiolabelin vivo. Further, PEGylated [125I]PVPh nanocarriers exhibited relatively long circulation half-lives (t1/2 α= 2.9 h, t1/2 β= 34.9 h) and gradual reticuloendothelial clearance, with 31% of injected dose in blood retained at 24 h post-injection.
authors.affiliation: Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ United States; Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA, United States.
authors.forename: Christina
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ United States; Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA, United States.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Edelstein
authors.affiliation: Department of Radiology, Division of Nuclear Medicine and Clinical Molecular Imaging.
authors.forename: John L
authors.initials: JL
authors.lastname: Mikitsh
authors.affiliation: Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ United States; Department of Radiology, Division of Nuclear Medicine and Clinical Molecular Imaging.
authors.forename: Edward
authors.initials: E
authors.lastname: Xiao
authors.affiliation: Department of Radiation Oncology.
authors.forename: Aaron H
authors.initials: AH
authors.lastname: Hemphill
authors.affiliation: Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Pagels
authors.affiliation: Department of Radiology, Division of Nuclear Medicine and Clinical Molecular Imaging; Department of Radiation Oncology.
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Chacko
authors.affiliation: Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Prud'homme
keywords: Flash NanoPrecipitation (FNP); biodistribution; nanocarrier; nanoparticle; radioiodine; self-assembly