Covalent Radiopharmaceuticals

Covalent bonding radiopharmaceuticals have been developed in some studies, but they all have obvious deficiencies, mainly due to their high lipophilicity and non-specific covalent bonding. These fatal defects make them completely unable to be used for targeted radionuclide therapy.

Traditional covalent nuclear drugs directly conjugates nuclides on the basis of covalent drugs, lacking rational design. We solve the sore points of targeted radionuclide therapy by adding covalent warheads to nuclear drugs. We can realize high uptake, long retention and strong curative effect through irreversible covalent binding .

First, we demonstrate the covalent mechanism at the molecular level. At the start, we did autoradiograph. The RDC-protein complex’s blots in autoradiograph highly matched that in Coomassie blue protein staining while covalent-warhead-blocked RDC seemed no binding. Then we used MS/MS and docking confirmed specific covalent binding sites.

And then we took it a step further in vivo. To our astonishment and delight, the images and therapeutic effect are rather beautiful. At 9 hours, you can see much higher accumulation on tumor, and clearer background.