Provided herein are methods for introducing fluorine atom onto a biomolecule comprising: (i) providing a linker comprising a thiol-reactive terminus and an azido/alkyne-reactive terminus (ii) reacting the thiol-reactive terminus of the linker with a biomolecule comprising at least one thiol group or a reactive derivative thereof and (iii) subsequently reacting the azido/alkyne-reactive terminus of the linker with a fluorine-substituted azide or alkyne respectively. Also provided are compositions and method of synthesis of bifunctional linkers and bioconjugates as well as radio-diagnostic agents comprising fluorine-labeled biomolecules.
