Photoactivatable Fluorescent Tags for Dual-Modality Positron Emission Tomography Optical Imaging.

Fluorescent protein conjugates are vital tools in a wide range of scientific disciplines from basic biochemical research to applications in clinical pathology and intraoperative surgery. We report the synthesis and characterization of photoactivatable fluorophores ( PhotoTags ) based on the functionalization of coumarin, fluorescein, BODIPY, rhodamine B, and cyanine dyes with a photochemically active aryl azide group. Photochemical labeling experiments using human serum albumin produced fluorescent proteins in high yields under irradiation with ultraviolet light for <15 min. We also synthesized DFO-RhodB-PEG 3 -ArN 3 ─a photoactivatable compound that can be radiolabeled with 89 Zr for applications in optical imaging and positron emission tomography. One-pot 89 Zr-radiolabeling and light-induced protein conjugation produced [ 89 Zr]ZrDFO-RhodB-PEG 3 -azepin-trastuzumab. Proof-of-concept studies in vitro and in vivo confirmed that [ 89 Zr]ZrDFO-RhodB-PEG 3 -azepin-trastuzumab is a potential dual-modality agent for detecting human epidermal growth factor receptor 2 (HER2/ neu ) expression. Overall, the PhotoTag technology represents a rapid, synthetically versatile, and user-friendly approach for generating novel protein conjugates.