ABSTRACT
Radiolabeled biomolecules with short half-life times are of increasing importance for positron emission tomography (PET) imaging studies. Herein, we demonstrate an improved and generalized method for synthesizing a [radiometal]-unsaturated aldehyde as a lysine-labeling probe that can be easily conjugated into various biomolecules through the RIKEN click reaction. As a case study, 68 Ga-PET imaging of U87MG xenografted mice is demonstrated by using the 68 Ga-DOTA-RGDyK peptide, which is selective to αV ß3 integrins.
Subject(s)
Gallium Radioisotopes/pharmacokinetics , Peptides/pharmacokinetics , Positron-Emission Tomography/methods , Radiopharmaceuticals/pharmacokinetics , Animals , Cell Line, Tumor , Gallium Radioisotopes/chemistry , Heterografts , Humans , Integrin alphaVbeta3/metabolism , Mice , Mice, Inbred BALB C , Peptides/chemistry , Tissue DistributionABSTRACT
The unsaturated ester aldehyde, (E)-3-alkoxycarbonyl-5-phenyl-2,4-dienal, was efficiently dimerized by applying the strain-promoted double-click reaction with sym-dibenzo-1,5-cyclooctadiene-3,7-diyne. The resulting dimerized probe was sequentially reacted first with one peptide molecule and then with a protein or the amino groups on the surface of a live cell through double azaelectrocyclization to achieve highly efficient bioconjugation.
Subject(s)
Aldehydes/chemistry , Alkynes/chemistry , Animals , Cell Survival , Cyclization , Dimerization , Esters , HeLa Cells , Humans , Mice , Peptides/chemistry , Serum Albumin/chemistryABSTRACT
Versatile method for living cell labeling has been established. Cell surfaces are initially biotinylated by azaelectrocyclization, and then treated with the fluorescence-labeled avidin or the anti-biotin antibody.