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  3. Tetrazine- trans-Cyclooctene Chemistry Applied to Fabricate Self-Assembled Fluorescent and Radioactive Nanoparticles for in Vivo Dual Mode Imaging

Tetrazine- trans-Cyclooctene Chemistry Applied to Fabricate Self-Assembled Fluorescent and Radioactive Nanoparticles for in Vivo Dual Mode Imaging

  • Bioconjug Chem. 2019 Mar 20;30(3):547-551. doi: 10.1021/acs.bioconjchem.9b00038.
Arthur H A M van Onzen 1,  Raffaella Rossin 2,  Albertus P H J Schenning 3,  Klaas Nicolay 4,  Lech-Gustav Milroy 1,  Marc S Robillard 2,  Luc Brunsveld 1
Affiliations

Affiliations

  • 1 Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems (ICMS) , Eindhoven University of Technology , P.O. Box 513, 5600 MB Eindhoven , The Netherlands.
  • 2 Tagworks Pharmaceuticals, c/o Radboud University Medical Center , Department of Nuclear Medicine and Radiology , P.O. Box 9101, 6500 HB Nijmegen , The Netherlands.
  • 3 Stimuli-responsive Functional Materials and Devices and Institute for Complex Molecular Systems , Eindhoven University of Technology , P.O. Box 513, 5600 MB Eindhoven , The Netherlands.
  • 4 Biomedical NMR, Department of Biomedical Engineering , Eindhoven University of Technology , P.O. Box 513, 5600 MB Eindhoven , The Netherlands.
PMID: 30731039 DOI: 10.1021/acs.bioconjchem.9b00038
Abstract

Multimodal imaging agents combine two or more imaging modalities into one probe. Self-assembling fluorescent nanoparticles are a promising class of modular multimodal imaging probes as they can allow easy blending of imaging and targeting modalities. Our group recently developed a class of self-assembling and intrinsically fluorescent small molecule-based nanoparticles (SMNPs) with excellent optical properties. In this article, we describe the efficient radiolabeling of these SMNPs via a two-step bioconjugation strategy involving the inverse-electron-demand Diels-Alder ligation between a tetrazine (Tz)-tagged radiolabel and a trans-cyclooctene (TCO)-tagged fluorescent small molecule building block of the SMNPs. Studies in mice revealed that the SMNPs are well tolerated and could be monitored by both radioactivity and fluorescence, thereby demonstrating the potential of SMNPs in optical and dual-mode imaging in vivo. The work also testifies to the utility of the Tz-TCO conjugation chemistry for the labeling of self-assembled nanoparticles.

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