In a groundbreaking study, Prof. Gilles Gasser’s team at Chimie ParisTech-PSL, in collaboration with Belgian researchers, successfully radiolabelled an anti-c-Met Nanobody® with rhenium-188 using bioorthogonal click chemistry. This innovative approach paves the way for gentler radiolabelling strategies for sensitive biomolecules.

In a recent article published in Chemical Science, the group of Prof. Gilles Gasser at the Institute of Chemistry for Life and Health Sciences at Chimie ParisTech-PSL, in collaboration with the group of Dr. Tomas Opsomer and Dr. Maarten Ooms at SCK-CEN in Belgium describes the first reported use of bioorthogonal click chemistry with rhenium-188 (¹⁸⁸Re) for radiolabelling of an anti-c-Met V_HH Nanobody®. While the [¹⁸⁸Re]Re(V) oxidation state is stable under physiological conditions, the labelling process typically requires harsh conditions, such as high temperatures and excess reducing agent. These are often incompatible with sensitive biomolecules. A “chelate-then-click” strategy was therefore employed to connect their ¹⁸⁸Re-labelled chelator and V_HH post-labelling using Strain-promoted Azide-Alkyne Click Chemistry reaction (SPAAC). A key highlight of this study is the successful optimisation of the [¹⁸⁸Re]Re(V)-radiolabelling of a chelator bearing an easily-reducible azide group. Overall, this work illustrates the potential of bioorthogonal click chemistry for radiolabelling biomolecules with ¹⁸⁸Re, although further optimisation or alternative radiolabelling strategies to enhance the molar activity are necessary to improve pharmacokinetics.

The article can be found here.

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