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|Title:||Detrimental Effects of Radiation on the Fluorescence of Fluorophores: Implications for Dual-Modality Imaging|
|Authors:||HERNANDEZ Reinier; HESKAMP Sandra; RIJPKEMA Mark; GOLDENBERG David; MCBRIDE William; MORGENSTERN Alfred; BRUCHERTSEIFER Frank; CAI Weibo; BOERMAN Otto|
|Citation:||EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING vol. 42 no. S1 p. S164; OP 394|
|Type:||Articles in periodicals and books|
|Abstract:||Aim: Despite the large interest on nuclear/optical multimodality imaging, the effect of radiation on the fluorescence properties of fluorophores remains unknown. Herein we determined the radiosensitivity of the near infrared dye IRDye800CW, and devised a strategy to ameliorate its negative impact for multimodality imaging. Materials and Methods: Buffered aqueous solutions of IRDye800CW were incubated in the presence of increasing activities of 111In, 68Ga, or 213Bi (γ, β, and α emitter, respectively) and its normalized fluorescence (λex=740 nm and λem=796 nm) was determined at different radiation exposure times. The radioprotective effect of three hydroxyl radical scavengers (ethanol, gentisic acid, and ascorbic acid (AA)), was examined. The impact of other factors such as activity concentration, temperature, type of buffer, and pH on the fluorescence properties of IRDye800CW was also determined. Similar experiments were conducted on RDC018, a DOTA-conjugated IRDye800CW-derivative used as multimodality imaging probe in pretargeting. Results: A significant decrease of the fluorescence of IRDye800CW was observed upon incubation with escalating activities of 111In, 68Ga or 213Bi. The effect was dependent on the amount of activity as well as the type of radiation, which supported our hypothesis of a free radical-mediated mechanism. 68Ga showed the largest radiolytic effect – the fluorescence signal of the fluorophore was reduced to background levels within 30 min incubation with 20 MBq of 68Ga-, followed by 111In and 213Bi. IRDye800CW and RDC018 presented similar radiosensitivity except for 213Bi-labelled RDC018, which exhibited enhanced radiolysis, presumably due to direct radiation damage induced by α particles. The addition of scavengers provided a concentration dependent radioprotective effect. Among all scavengers, AA provided the most robust protection over a wide range of concentrations and preserved RDC018 fluorescence at much higher activity levels. Interestingly, AA afforded only partial radioprotection of 213Bi-RDC018, which further supported our hypothesis of α particle-fluorophore direct interaction. Conclusion: Herein we provide the first report on the radiosensitivity of fluorophores, and outline a set of conditions that minimize the deleterious effects of radiation damage on nuclear/optical multimodality imaging probes.|
|JRC Directorate:||Nuclear Safety and Security|
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