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Cross‐Isotopic Bioorthogonal Tools as Molecular Twins for Radiotheranostic Applications
Author(s) -
Rosecker Veronika,
Denk Christoph,
Maurer Melanie,
Wilkovitsch Martin,
Mairinger Severin,
Wanek Thomas,
Mikula Hannes
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900042
Subject(s) - bioorthogonal chemistry , pretargeting , tetrazine , chemistry , biodistribution , combinatorial chemistry , moiety , pharmacokinetics , click chemistry , computational biology , nanotechnology , in vitro , pharmacology , biochemistry , stereochemistry , organic chemistry , materials science , medicine , antibody , radioimmunotherapy , immunology , monoclonal antibody , biology
Radiotheranostics are designed by labeling targeting (bio)molecules with radionuclides for diagnostic or therapeutic application. Because the pharmacokinetics of therapeutic compounds play a pivotal role, chemically closely related imaging agents are used to evaluate the overall feasibility of the therapeutic approach. “Theranostic relatives” that utilize different elements are frequently used in clinical practice. However, variations in pharmacokinetics, biodistribution, and target affinity due to different chemical properties of the radioisotopes remain as hurdles to the design of optimized clinical tools. Herein, the design and synthesis of structurally identical compounds, either for diagnostic ( 18 F and a stable metal isotope) or therapeutic application (radiometal and stable 19 F), are reported. Such “molecular twins” have been prepared by applying a modular strategy based on click chemistry that enables efficient radiolabeling of compounds containing a metal complex and a tetrazine moiety. This additional bioorthogonal functionality can be used for subsequent radiolabeling of (bio)molecules or pretargeting approaches, which is demonstrated in vitro.