Development of Polar BODIPY-Tetrazines for Rapid Pretargeted Fluorescence Imaging

Markus Staudt; Lars Hvass; Marius Müller; Rocío García-Vázquez; Jesper Tranekjær Jo Rgensen; Vladimir Shalgunov; Umberto Maria Battisti; Andreas Kjær; Matthias M Herth

doi:10.1021/acsomega.4c06570

Development of Polar BODIPY-Tetrazines for Rapid Pretargeted Fluorescence Imaging

ACS Omega. 2024 Sep 30;9(41):42498-42505. doi: 10.1021/acsomega.4c06570. eCollection 2024 Oct 15.

Authors

Markus Staudt¹, Lars Hvass^{2

3}, Marius Müller¹, Rocío García-Vázquez¹, Jesper Tranekjær Jo Rgensen^{2

3}, Vladimir Shalgunov^{1

2}, Umberto Maria Battisti¹, Andreas Kjær^{2

3}, Matthias M Herth^{1

2}

Affiliations

¹ Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
² Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
³ Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, 2100 Copenhagen, Denmark.

Abstract

Polar BODIPY-tetrazine dyes were developed and clicked in vivo to a preaccumulated trans-cyclooctene-modified anti-TAG72 monoclonal antibody CC49 (CC49-TCO). The in vivo click performance was evaluated using an in-house developed ex vivo blocking assay. All tested polar BODIPY structures exhibited excellent in vivo binding, confirming that the turn-on tetrazine dyes successfully clicked in vivo to pretargeted CC49-TCO. Fluorescence imaging showed high tumor-to-muscle ratios of 4:1. This proof-of-concept study indicates that the pretargeting concept based on turn-on probes could be used for cancer treatments, such as photodynamic or -thermal therapy.