Controllable stripping of radiolabeled group in vivo to optimize nuclear imaging via NO-responsive bioorthogonal cleavage reaction

A novel “turn-off” strategy for controllable radionuclide clearance is established. 1,4-dihydropyridine (DHP) is used as a conditional linker to connect a radioisotope labeled moiety and nano-agent. A highly specific, sensitive and effective C–C bond cleavage of DHP happens in vivo when treated with nitric oxide which is provided by glyceryl trinitrate (GTN). The radioactive cut-off part from the nanoparticle is observed to be cleared quickly by microSPECT-CT. 3–5 times decreases of radioactivity in the blood, kidneys, intestine, heart and lungs are observed after GTN treatment in a biodistribution assay. The radioactivity redistribution indicates that the radioactive leaving part is indeed cut off and the radionuclide metabolism accelerated. Organ level internal dose assessment reveals the GTN treated groups carry only ½ the radiation dose of the control group. Collectively, a feasible pathway for controllable radionuclide clearance is for the first time provided for high contrast and low radiation nuclear imaging.