99mTc and 111In-Labeling of Small Biomolecules: Bifunctional Chelators and Related Coordination Chemistry

Radiolabeled small biomolecules provide a unique tool for target-specific delivery of radionuclides to the diseased tissues and have emerged as promising candidates in molecular imaging and radiotherapy of cancers. 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 the radiotracer's pharmacokinetics. 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 biological properties of the target-specific radiopharmaceutical, its in vivo pharmacokinetics can be altered by modifying the coordination environment with various chelators or coligand. Among various SPECT radionuclides, Tc-99m remains to be the most prominent radionuclide for the development of diagnostic radiopharmaceuticals because of its ideal nuclear properties and easy availability at low cost. In-111 is also widely used in gamma scintigraphy (only second to Tc-99m). In addition, In-111-labeld radiotracers are often used as the imaging surrogates for biodistribution and dosimetry determination of their corresponding Y-90 analogs due to their similar coordination chemistry. This chapter will focus on the on the use of different BFCs for Tc-99m and In-111-labeling of small biomolecules and the related coordination chemistry.