Development of a clickable bimodal fluorescent/PET probe for in vivo imaging

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Abstract

Background: Fluorescent imaging agents are becoming evermore important in preclinical and clinical research. They do, however, suffer from poor tissue penetration, which makes optical fluorescence imaging incompatible with whole-body imaging techniques. The design of novel bimodal PET active and fluorescent tracers could therefore combine the benefits of optical imaging with radioactively labeled imaging probes. Herein, we report the synthesis and evaluation of a clickable 18 F-labeled fluorescent dye. Methods: An azide-modified BODIPY-Fl dye could be successfully radio-labeled with 18 F using an 18 F/ 19 F exchange reaction of the boron-fluoride core of the BODIPY dye to yield a clickable bimodal PET/fluorescent imaging tool. In vitro as well as in vivo imaging (PET/fluorescence) using a bombesin analog was conducted to study the applicability of the dual-modality imaging probe. Results: We use the radio-labeled small molecule, 18 F-BODIPY-azide to label site-specifically different targeted peptides, based on a standard modular labeling protocol. Following the synthesis of a bimodal bombesin analog, we determine the peptide tracer’s performance in vitro and in vivo, exploring both the optical as well as PET imaging capabilities. Conclusion: This versatile methodology has the potential to have a transformational impact on 18 F radiotracer synthesis, opening the door for rapid screening of novel-labeled peptide tracers, both on the cellular (optical) as well as whole-body (PET) level.

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Paulus, A., Desai, P., Carney, B., Carlucci, G., Reiner, T., Brand, C., & Weber, W. A. (2015). Development of a clickable bimodal fluorescent/PET probe for in vivo imaging. EJNMMI Research, 5(1). https://doi.org/10.1186/s13550-015-0120-4

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