title: Preventing Radiobleaching of Cyanine Fluorophores Enhances Stability of Nuclear/NIRF Multimodality Imaging Agents.
abstract: Despite the large interest in nuclear/optical multimodality imaging, the effect of radiation on the fluorescence of fluorophores remains largely unexplored. Herein, we report on the radiobleaching of cyanine fluorophores and describe conditions to provide robust radioprotection under practical (pre)clinical settings. We determined the radiosensitivity of several cyanine fluorescent compounds, including IRDye 800CW (800CW) and a dual modality imaging tetrapeptide containing DOTA as chelator and Dylight 800 as fluorophore, exposed to increasing activities of111In,68Ga, or213Bi (γ, EC/β, and α emitter, respectively). An activity and type of radiation-dependent radiation-induced loss of fluorescence, radiobleaching, of 800CW was observed upon incubation with escalating activities of111In,68Ga, or213Bi.68Ga showed the largest radiolytic effect, followed by111In and213Bi. The addition of oxygen radical scavengers including ethanol, gentisic acid, and ascorbic acid (AA), provided a concentration dependent radioprotective effect. These results supported the hypothesis of a free radical-mediated radiobleaching mechanism. AA provided the most robust radioprotection over a wide range of concentrations and preserved fluorescence at much higher radioactivity levels. Overall, both near-infrared fluorescent compounds displayed similar sensitivity, except for213Bi-irradiated solutions, where the dual modality construct exhibited enhanced radiolysis, presumably due to direct radiation damage from α particles. Concurrently, AA was not able to preserve fluorescence of the dual-modality molecule labeled with213Bi. Our findings have important consequences for several research areas including ROS sensing, radiation-mediated drug release (uncaging), fluorescent dosimetry, and in the preparation of dual-modality radiopharmaceuticals.
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Medical Physics, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Reinier
authors.initials: R
authors.lastname: Hernandez
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: Heskamp
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Rijpkema
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Desirée L
authors.initials: DL
authors.lastname: Bos
authors.affiliation: Immunomedics, Morris Plains, NJ, United States.
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.affiliation: Immunomedics, Morris Plains, NJ, United States.
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
authors.affiliation: European Commission, Joint Research Centre - Directorate for Nuclear Safety and Security, Karlsruhe, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: Morgenstern
authors.affiliation: European Commission, Joint Research Centre - Directorate for Nuclear Safety and Security, Karlsruhe, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Bruchertseifer
authors.affiliation: Department of Medical Physics, University of Wisconsin, Madison, Wisconsin, USA.; Department of Radiology, University of Wisconsin, Madison, WI, USA.; University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
mesh_terms: D005456:Fluorescent Dyes / Q000378:metabolism*; D064847:Multimodal Imaging / Q000379:methods*; D061848:Optical Imaging / Q000379:methods*; D011859:Radiography / Q000379:methods*; D011868:Radioisotopes / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D011868:Radioisotopes
keywords: multimodality imaging; nuclear-optical imaging; radical scavengers.; radiobleaching; radioprotection