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 m...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-PEG_(4)-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-PEG_(4)-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.展开更多
基金funding from the EPSRC Centre for Doctoral Training in Smart Medical Imaging(EP/S022104/1)the Department of Bioengineering,Imperial College London+4 种基金supported by funding from the EPSRC grant(EP/X01374X/1)funding from the Rosetrees Trust and the John Black Charitable Foundation(Grant No.A2200)supported by an Imperial College London President’s Scholarship.S.V.M.acknowledges funding from her Imperial College Research Fellowship.M.F.L.received funding from Cancer Research UK(No.190133,DRCMDP-Nov24/100005)the Rosetrees Trust and the John Black Charitable Foundation(Grant No.A2200)the Brain Tumour Charity(Grant No.QfC_2018_10387).
文摘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-PEG_(4)-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-PEG_(4)-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.
