Bifunctional coupling agents for radiolabeling of biomolecules and target-specific delivery of metallic radionuclides

Adv Drug Deliv Rev. 2008 Sep;60(12):1347-70. doi: 10.1016/j.addr.2008.04.006. Epub 2008 Apr 23.


Receptor-based radiopharmaceuticals are of great current interest in molecular imaging and radiotherapy of cancers, and provide a unique tool for target-specific delivery of radionuclides to the diseased tissues. In general, a target-specific radiopharmaceutical can be divided into four parts: targeting biomolecule (BM), pharmacokinetic modifying (PKM) linker, bifunctional coupling or chelating agent (BFC), and radionuclide. The targeting biomolecule serves as a "carrier" for specific delivery of the radionuclide. PKM linkers are used to modify radiotracer excretion kinetics. BFC is needed for radiolabeling of biomolecules with a metallic radionuclide. Different radiometals have significant difference in their coordination chemistry, and require BFCs with different donor atoms and chelator frameworks. Since the radiometal chelate can have a significant impact on physical and biological properties of the target-specific radiopharmaceutical, its excretion kinetics can be altered by modifying the coordination environment with various chelators or coligand, if needed. This review will focus on the design of BFCs and their coordination chemistry with technetium, copper, gallium, indium, yttrium and lanthanide radiometals.

Publication types

  • Review

MeSH terms

  • Animals
  • Copper Radioisotopes / administration & dosage
  • Copper Radioisotopes / chemistry
  • Drug Delivery Systems*
  • Gallium Radioisotopes / administration & dosage
  • Gallium Radioisotopes / chemistry
  • Humans
  • Indium Radioisotopes / administration & dosage
  • Indium Radioisotopes / chemistry
  • Isotope Labeling
  • Organotechnetium Compounds / administration & dosage
  • Organotechnetium Compounds / chemistry
  • Radioisotopes / administration & dosage*
  • Radioisotopes / chemistry
  • Radiopharmaceuticals / administration & dosage*
  • Radiopharmaceuticals / chemistry
  • Yttrium Radioisotopes / administration & dosage
  • Yttrium Radioisotopes / chemistry


  • Copper Radioisotopes
  • Gallium Radioisotopes
  • Indium Radioisotopes
  • Organotechnetium Compounds
  • Radioisotopes
  • Radiopharmaceuticals
  • Yttrium Radioisotopes