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Pretargeted imaging beyond the blood-brain barrier.
Vladimir Shalgunov1, Sara Lopes van den Broek1, Ida Vang Andersen1
1Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen Universitetsparken 2 2100 Copenhagen Denmark umberto.battisti@sund.ku.dk matthias.herth@sund.ku.dk.
RSC Medicinal Chemistry
|March 27, 2023
Summary
We developed novel fluorine-18 labeled tetrazines for pretargeted imaging beyond the blood-brain barrier. This breakthrough enables in vivo imaging of brain targets, advancing neuroimaging and diagnostics.
Area of Science:
- Nuclear medicine
- Bioorthogonal chemistry
- Neuroimaging
Background:
- Pretargeting enhances imaging contrast and reduces radiation dose.
- Tetrazine ligation with trans-cyclooctene is a key bioorthogonal reaction.
- Pretargeted imaging beyond the blood-brain barrier (BBB) remains a significant challenge.
Purpose of the Study:
- To develop novel fluorine-18 labeled tetrazines for pretargeted imaging beyond the BBB.
- To enable in vivo bioorthogonal reactions within the brain.
- To establish a foundation for pretargeted neuroimaging of currently inaccessible targets.
Main Methods:
- Rational drug design incorporating BBB penetration, contrast, and metabolism parameters.
- Synthesis and evaluation of 18F-labeled tetrazines.
- In vivo testing of tetrazine ligation efficiency with trans-cyclooctene in the brain.
Main Results:
- Five 18F-labeled tetrazines demonstrated in vivo click performance in the brain.
- [18F]18 exhibited the most favorable characteristics for brain pretargeting.
- The lead compound [18F]18 is suitable for future pretargeted neuroimaging studies.
Conclusions:
- Pretargeting beyond the BBB is achievable with 18F-labeled tetrazines.
- This approach opens avenues for imaging soluble protein oligomers and other neurodegeneration biomarkers.
- Enables early diagnosis, personalized treatment monitoring, and accelerated drug development in neurology.
