Cross‐Isotopic Bioorthogonal Tools as Molecular Twins for Radiotheranostic Applications

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 t...

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Bibliographic Details
Published in:Chembiochem : a European journal of chemical biology 2019-06, Vol.20 (12), p.1530-1535
Main Authors: Rosecker, Veronika, Denk, Christoph, Maurer, Melanie, Wilkovitsch, Martin, Mairinger, Severin, Wanek, Thomas, Mikula, Hannes
Format: Article
Language:English
Subjects:
bioorthogonal chemistry
Chemical compounds
Chemical properties
Chemical synthesis
click chemistry
Click Chemistry - methods
Communication
Communications
Coordination compounds
Design optimization
Diagnostic software
Diagnostic systems
Feasibility studies
Humans
Isotope Labeling - methods
isotopes
Metals
Organic chemistry
Pharmacokinetics
Pharmacology
radiochemistry
Radioisotopes
Radiolabelling
radiopharmaceuticals
Radiopharmaceuticals - chemical synthesis
Radiopharmaceuticals - chemistry
Theranostic Nanomedicine - methods
Tissue Distribution
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Summary: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 (18F and a stable metal isotope) or therapeutic application (radiometal and stable 19F), 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. Chemical lookalikes: A modular approach for the synthesis of chemically identical “cross‐isotopic” agents for theranostic applications is reported. These compounds contain a chelator for the introduction of therapeutic radiometals or the respective stable metal isotopes, and can be labeled with 18F or stable 19F by click chemistry.
ISSN:1439-4227
1439-7633
1439-7633
DOI:10.1002/cbic.201900042