title: Nontoxic Formulations of Scintillation Nanocrystals for Use as X-ray Computed Tomography Contrast Agents.
abstract: X-ray computed tomography (CT) is currently one of the most powerful, noninvasive, clinical in vivo imaging techniques, which has resulted from advances in both X-ray device and contrast enhancement technologies. The present study demonstrates, for the first time, that metal tungstates (such as CaWO4) are promising contrast agents for X-ray, radiation, and CT imaging, because of the high X-ray mass attenuation of tungsten (W). We have developed a method of formulation, in which CaWO4(CWO) nanoparticles (NPs) are encapsulated within a biocompatible poly(ethylene glycol-b-d,l-lactic acid) (PEG-PLA) block copolymer (BCP) capsule. We show that these PEG-PLA-encapsulated CWO NPs (170 ± 10 nm hydrodynamic diameter) produce a higher CT contrast (by a factor of about 2) than commercial iodine-based radiocontrast agents (e.g., Iohexol) at identical molar concentrations of W or I atoms. PEG-PLA-coated CWO NPs are chemically stable and completely nontoxic. It was confirmed that the maximum tolerated dose (MTD) of this material in mice is significantly higher (250 ± 50 mg per kg body weight following a single intravenous (IV) administration) than, for instance, commercially available dextran-coated iron oxide nanoparticles that are currently used clinically as MRI contrast agents (MTD in mice ≈ 168 mg/kg per dose IV). IV-injected PEG-PLA/CWO NPs caused no histopathologic damage in major excretory organs (heart, liver, lungs, spleen, and kidney). When an IV dose of 100 mg/kg was given to mice, the blood circulation half-life was measured to be about 4 h, and more than 90% of the NPs were cleared from the mice within 24 h via the renal and hepatobiliary systems. When intratumorally administered, PEG-PLA-coated CWO NPs showed complete retention in a tumor-bearing mouse model (measurements were made up to 1 week). These results suggest that PEG-PLA-coated CWO NPs are promising materials for use in CT contrast.
authors: School of Chemical Engineering, ‡Department of Veterinary Clinical Sciences, §Department of Comparative Pathobiology, and ∥Purdue University Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors: Jaewon
authors: J
authors: Lee
authors: School of Chemical Engineering, ‡Department of Veterinary Clinical Sciences, §Department of Comparative Pathobiology, and ∥Purdue University Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors: Seulgi
authors: S
authors: Choi
authors: School of Chemical Engineering, ‡Department of Veterinary Clinical Sciences, §Department of Comparative Pathobiology, and ∥Purdue University Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors: Ki Hyun
authors: KH
authors: Kim
authors: School of Chemical Engineering, ‡Department of Veterinary Clinical Sciences, §Department of Comparative Pathobiology, and ∥Purdue University Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors: Hock Gan
authors: HG
authors: Heng
authors: School of Chemical Engineering, ‡Department of Veterinary Clinical Sciences, §Department of Comparative Pathobiology, and ∥Purdue University Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors: Sandra E
authors: SE
authors: Torregrosa-Allen
authors: School of Chemical Engineering, ‡Department of Veterinary Clinical Sciences, §Department of Comparative Pathobiology, and ∥Purdue University Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors: Benjamin S
authors: BS
authors: Ramsey
authors: School of Chemical Engineering, ‡Department of Veterinary Clinical Sciences, §Department of Comparative Pathobiology, and ∥Purdue University Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors: Bennett D
authors: BD
authors: Elzey
authors: School of Chemical Engineering, ‡Department of Veterinary Clinical Sciences, §Department of Comparative Pathobiology, and ∥Purdue University Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors: You-Yeon
authors: YY
authors: Won
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D053758:Nanoparticles; D012588:Scintillation Counting; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D003287:Contrast Media