Abstract
Inorg Chem Front. 2025 Oct 14. doi: 10.1039/d5qi01745a. Online ahead of print.
ABSTRACT
Lanthanide chelates and copper-free 'click' chemistry have important uses for targeted molecular imaging and therapeutic strategies. Herein, we report the complexation of lanthanides to a tetrazine-functionalised DO3A macrocyclic chelator and the tetrazine-TCO ligation between the lanthanide(DO3A-tetrazine) complexes and a TCO-PEG4-functionalised rhodamine as a model agent. The luminescent and magnetic properties of the resultant dual-modal conjugates are described. The tetrazine moiety was found to sensitise terbium luminescence, resulting in a 'turn-off' effect upon its transformation to the dihydropyridazine linker, with the rhodamine moiety then dominating the fluorescence emissions. The T 1 relaxivities of Gd(DO3A-tetrazine) and Gd(DO3A-PEG4-rhodamine) were found to be similar to [Gd(DOTA)]- (Dotarem®). As a proof-of-concept in vivo test, the click conjugates were delivered to mice brains using the combination of focused ultrasound and microbubbles, with neuron uptake of the probes observed.
PMID:41132234 | PMC:PMC12542886 | DOI:10.1039/d5qi01745a