Recent Advances in 99 mTc

Technetium-99m (99mTc) is one of the most desirable radionuclides for external imaging in diagnostic nuclear medicine, due to the emission of gamma ray of optimal energy (140 keV), a suitable half-life (6 h), and availability from 99Mo-99mTc generator systems. In addition, development of 99mTc radiopharmaceuticals for tumor imaging paves the way for therapeutic radiopharmaceuticals with high energy beta emitters 186Re and 188Re because of similar chemical properties between technetium and rhenium. Technetium (Z = 43) is situated in the middle of the second-row transition series and has no stable isotopes, which retarded the development of its chemistry. At the initial stage of 99mTc radiopharmaceutical development, major efforts were focused on imaging bone and excretory organs such as the liver and kidney, since it was thought that Tc is a foreign substance and recognized as such by the body. In 1982, Yokoyama et al. reported that a 99mTc-dithiosemicarbazone complex (a Tc-N2S2 type complex) with a glucose backbone (Fig. 1A) could penetrate the intact blood-brain barrier of laboratory animals.1,2 They also reported that 99mTc-dithiosemicarbazone complexes appended with a tertiary (Fig. 1B) or a quarternary amine group showed myocardial uptake.1,3 These findings encouraged further efforts to develop 99mTc radiopharmaceuticals for brain and myocardial functions. Meanwhile, the Davison and Jones group made another important finding in technetium chemistry, demonstrating that pentavalent oxotechnetium (5+) forms a five-coordinated mononuclear complex of high stability with a N2S2 ligand (Fig. 1C).4 They also developed the first organometallic low-oxidation state Tc(I) hexakis(isonitrile) complex (Fig. 1D), which constituted a prototype compound for the currently used myocardial perfusion agent, 99mTc(I) hexakis(2-methoxyisobutylisonitrile).5 These chemical studies stimulated the development of another class of mononuclear Recent advances in 99mTc radiopharmaceuticals