Receptor-targeted technetium-99m radiopharmaceuticals: increasing access to molecular imaging in healthcare

The γ-emitting radionuclide, technetium-99m ( 99m Tc), is widely accessible from 99m Tc generators, and is routinely incorporated into diagnostic imaging radiopharmaceuticals that measure perfusion or anatomical process in disease. There is potential to expand the use of 99m Tc to molecular radiopharmaceuticals, and leverage well-established and existing nuclear medicine infrastructure and resources (including nuclear reactor and 99m Tc generator supply chains, radiopharmacies, γ-scintigraphy and SPECT cameras, and trained nuclear medicine staff) to increase patient access to the benefits of receptor-targeted molecular imaging, particularly in oncology. To achieve this, suitable chemistry is required to develop new 99m Tc-labelled radiopharmaceuticals that incorporate 99m Tc into biomolecules. This review describes how existing 99m Tc chemistry has recently been applied to such innovations: chelator and ligand motifs (including mercapto-peptide, amine oxine, phosphine, isonitriles) that are already used for kit-based synthesis of 99m Tc perfusion agents have been derivatised with biomolecular pharmacophores for receptor-targeted molecular imaging. Recent clinical trials have established an evidence basis illustrating the utility of these new receptor-targeted 99m Tc radiopharmaceuticals. This work also describes the potential for an economical companion “theranostic” approach with the β - -emitter, rhenium-188 ( 188 Re), which can also be produced using generator technology. Initial preclinical and clinical studies have demonstrated that chemically analogous 99m Tc and 188 Re radiotracers show highly similar biodistribution patterns.