Technetium-99m and rhenium-188 complexes with one and two pendant bisphosphonate groups for imaging arterial calcificationElectronic supplementary information (ESI) available. See DOI: 10.1039/c4dt02965h

The first 99m Tc and 188 Re complexes containing two pendant bisphosphonate groups have been synthesised, based on the mononuclear M( v ) nitride core with two dithiocarbamate ligands each with a pendant bisphosphonate. The structural identity of the 99 Tc and stable rhenium analogues as uncharged, mononuclear nitridobis(dithiocarbamate) complexes was determined by electrospray mass spectrometry. The 99m Tc complex showed greater affinity for synthetic and biological hydroxyapatite, and greater stability in biological media, than the well-known but poorly-characterised and inhomogeneous bone imaging agent 99m Tc-MDP. It gave excellent SPECT images of both bone calcification (mice and rats) and vascular calcification (rat model), but the improved stability and the availability of two pendant bisphosphonate groups conferred no dramatic advantage in imaging over the conventional 99m Tc-MDP agent in which the bisphosphonate group is bound directly to Tc. The 188 Re complex also showed preferential uptake in bone. These tracers and the biological model of vascular calcification offer the opportunity to study the biological interpretation and clinical potential of radionuclide imaging of vascular calcification and to deliver radionuclide therapy to bone metastases. The synthesis of the first technetium-99m and rhenium-188 complexes with two pendant bisphosphonate groups is described, along with their in vivo use in imaging the skeleton and arterial calcification.