Synthesis of [¹⁸F]BODIPY: Bifunctional Reporter for Hybrid Optical/Positron Emission Tomography Imaging

Fluorescence-based intravital imaging approaches have been essential for studying the function and distribution of biologically active small molecules and their molecular targets in vivo.[1] While optical imaging enables visualization over a broad scope of spatial resolution ranging from subcellular to whole body anatomical imaging, its application is constrained by the optical transparency of tissues. Optical imaging modalities are thus better suited for small animal imaging rather than for translational applications.[2] In contrast, Positron Emission Tomography (PET) is used routinely for clinical applications but its use is limited primarily to macroscopic spatial and temporal imaging. A strategy that would enable seamless switching between fluorescence and PET imaging would thus be highly desirable for several reasons. First, the ability to visualize PET probes at the microscopic level would allow more rapid validation of the former in vivo and consequently expedite the development of novel PET probes. Second, for macroscopic hybrid imaging[3], it would be possible for optical and PET signals to be superimposed onto structural information derived from magnetic resonance imaging (MRI) or computed tomography (CT). Likewise, the ability to image in more than one or two channels would be useful for visualizing underlying physiological events. Third, hits from microscopic screens of small molecule fluorochrome-adducts could be more rapidly translated into clinically relevant applications.