Role of Pure Technetium Chemistry: Are There Still Links to Applications in Imaging?

The discovery and development of new ^99mTc-based radiopharmaceuticals or labeled drugs in general is based on innovative, pure chemistry and subsequent, application-targeted research. This was the case for all currently clinically applied imaging agents. Most of them were market-introduced some 20 years ago, and the few more recent ones are based on even older chemistry, albeit technetium chemistry has made substantial progress over the last 20 years. This progress though is not mirrored by new molecular imaging agents and is even accompanied by a steady decrease in the number of groups active in pure and applied technetium chemistry, a contrast to the trends in most other fields in which d-elements play a central role. The decrease in research with technetium has been partly counterbalanced by a strong increase of research activities with homologous, cold rhenium compounds for therapy, disclosing in the future eventually a quite unique opportunity for theranostics. This Viewpoint analyzes the pathways that led to radiopharmaceuticals in the past and their underlying fundamental contributions. It attempts to tackle the question of why new chemistry still does not lead to new imaging agents, i.e., the question of whether pure technetium chemistry is still needed at all.