New organometallic technetium complexes for radiopharmaceutical imaging

It is the objective of this review to introduce the reader to the current status of organometallic chemistry, oriented towards the development of novel Tc-99m-based imaging agents. This type of inorganic chemistry has nowadays become part of so-called bioorganometallic chemistry. The article describes the current state of research and development of radiopharmaceutical imaging agents based on organometallic: moieties and complexes. Organometallics are, in general, not considered to play an important role in inorganic medicinal chemistry. An introductory section describes the requirements for practical application of a radiopharmaceutical to underline in the second part that currently available compounds might wen be the basis for the development of completely new imaging agents. The introduction gives also a short outline of basic organometallic technetium compounds as well as organometallic aqua ions from other elements which are currently under investigation in the new field of bioorganometallic chemistry. In the following section, major focus is put on technetium-CO complexes. The compound [Tc-99m(OH2)(3)(CO)(3)](+) is the prototype of a precursor, the special behaviour of which is based on its organometallic character. The synthesis and some fundamental properties are discussed. Within this section substitution reactions of [Tc-99m(OH2)(3)(CO)(3)](+) are presented according to the denticity of the ligands. The reactions are critically highlighted in respect of their versatility for the development of novel radiopharmaceuticals. Combining monodentate and bidentate ligands leads to the potential of a new [2+1] mixed-ligand concept. In the last section, the labelling of biomolecules with organometallic moieties is described. Since most of the organometallic complexes are still being researched this section focuses on concepts, and some of the most important developments towards new CNS receptor ligands and labelled peptides and proteins are given. This section aims at motivating researchers from radiopharmaceutical chemistry to experience new approaches which are probably superior to the currently available ones. Throughout the text, examples from other organometallic compounds are described; however, since the carbonyl concept is the most advanced, the review is oriented towards the chemistry of [Tc-99m(OH2)(3)(CO)(3)](+).