Cysteine-selective [¹⁸⁸Re]Re(v) radiolabelling of a Nanobody® for targeted radionuclide therapy using a "chelate-then-click" approach.

ABSTRACT: In this study, we present the first reported use of bioorthogonal click chemistry with rhenium-188 for radiolabelling of an anti-c-Met V_HH Nanobody®. We employed a "chelate-then-click" strategy, wherein a bifunctional chelator was designed in two parts, which were subsequently joined post-labelling and post-conjugation via the strain-promoted azide-alkyne cycloaddition (SPAAC) reaction. Cysteine-selective conjugation of the V_HH was achieved through thiol-Michael addition, forming a V_HH-DBCO construct. Radiolabelling of the azide-functionalised chelator with [¹⁸⁸Re]Re(v) was optimised to achieve a radiochemical conversion of ∼70%, despite challenges associated with maintaining the azide functionality under reducing conditions. The final pro

SUBMITTER: Melis DR 

PROVIDER: S-EPMC11894466 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature