Theranostics 2017; 7(1):1-8. doi:10.7150/thno.15124 This issue Cite

Short Research Communication

Preventing Radiobleaching of Cyanine Fluorophores Enhances Stability of Nuclear/NIRF Multimodality Imaging Agents

Reinier Hernandez1,2, Sandra Heskamp1, Mark Rijpkema1, Desirée L. Bos1, David M. Goldenberg3, William J. McBride3, Alfred Morgenstern4, Frank Bruchertseifer4, Weibo Cai2,5,6, Otto C. Boerman1✉

1. Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
2. Department of Medical Physics, University of Wisconsin, Madison, Wisconsin, USA.
3. Immunomedics, Morris Plains, NJ, United States.
4. European Commission, Joint Research Centre - Directorate for Nuclear Safety and Security, Karlsruhe, Germany.
5. Department of Radiology, University of Wisconsin, Madison, WI, USA.
6. University of Wisconsin Carbone Cancer Center, Madison, WI, USA.

Citation:
Hernandez R, Heskamp S, Rijpkema M, Bos DL, Goldenberg DM, McBride WJ, Morgenstern A, Bruchertseifer F, Cai W, Boerman OC. Preventing Radiobleaching of Cyanine Fluorophores Enhances Stability of Nuclear/NIRF Multimodality Imaging Agents. Theranostics 2017; 7(1):1-8. doi:10.7150/thno.15124. https://www.thno.org/v07p0001.htm
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Abstract

Graphic 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 of 111In, 68Ga, or 213Bi (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 of 111In, 68Ga, or 213Bi. 68Ga showed the largest radiolytic effect, followed by 111In and 213Bi. 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 for 213Bi-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 with 213Bi. 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.

Keywords: radiobleaching, multimodality imaging, nuclear-optical imaging, radioprotection, radical scavengers.


Citation styles

APA
Hernandez, R., Heskamp, S., Rijpkema, M., Bos, D.L., Goldenberg, D.M., McBride, W.J., Morgenstern, A., Bruchertseifer, F., Cai, W., Boerman, O.C. (2017). Preventing Radiobleaching of Cyanine Fluorophores Enhances Stability of Nuclear/NIRF Multimodality Imaging Agents. Theranostics, 7(1), 1-8. https://doi.org/10.7150/thno.15124.

ACS
Hernandez, R.; Heskamp, S.; Rijpkema, M.; Bos, D.L.; Goldenberg, D.M.; McBride, W.J.; Morgenstern, A.; Bruchertseifer, F.; Cai, W.; Boerman, O.C. Preventing Radiobleaching of Cyanine Fluorophores Enhances Stability of Nuclear/NIRF Multimodality Imaging Agents. Theranostics 2017, 7 (1), 1-8. DOI: 10.7150/thno.15124.

NLM
Hernandez R, Heskamp S, Rijpkema M, Bos DL, Goldenberg DM, McBride WJ, Morgenstern A, Bruchertseifer F, Cai W, Boerman OC. Preventing Radiobleaching of Cyanine Fluorophores Enhances Stability of Nuclear/NIRF Multimodality Imaging Agents. Theranostics 2017; 7(1):1-8. doi:10.7150/thno.15124. https://www.thno.org/v07p0001.htm

CSE
Hernandez R, Heskamp S, Rijpkema M, Bos DL, Goldenberg DM, McBride WJ, Morgenstern A, Bruchertseifer F, Cai W, Boerman OC. 2017. Preventing Radiobleaching of Cyanine Fluorophores Enhances Stability of Nuclear/NIRF Multimodality Imaging Agents. Theranostics. 7(1):1-8.

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