Development of Technetium-99m and Rhenium-188 Radiopharmaceuticals Containing a Terminal Metal-Nitrido Multiple Bond for Diagnosis and Theraphy

The chemistry of nitrido complexes of technetium has played an important role in the search of new Tc-99m radiopharmaceuticals and in providing efficient labeling procedures of biologically active molecules. A number of potentially useful 99mTc-labeled nitrido compounds have been found for imaging the most important organs and, in particular, for heart imaging. The relevance of nitrido complexes is also currently expanding to the field of Re-188 radiopharmaceuticals utilized as therapeutic agents in the treatment of degenerative diseases. Presumably, the most useful characteristic of nitrido complexes of technetium and rhenium lies in their unique structural features that are strictly controlled by the electronic structure of the TcN multiple bond. Five-coordination is the most common arrangement, and structures may range between the two ideal limits of square pyramidal and trigonal bipyramidal geometry. It was found that geometrical changes can be efficiently manipulated through the careful selection of the type of coordinating atoms bound to the TcN group. A set of four -donor atoms favors square pyramidal geometry, while a combination of two donors and two acceptors causes the structure to switch toward trigonal bipyramidal geometry. The precise geometrical control conjoined with the high stability of the TcN group easily allows a rational design of different categories of radiopharmaceuticals and the determination of their structure-activity relationships. In turn, this makes possible a fine tuning of the biological properties of selected lead compounds. In this review, a summary of the more recent results obtained in the application of nitrido complexes of technetium and rhenium to nuclear medicine and molecular imaging will be given with specific emphasis to the underlying chemical principles.