title: Technetium-99m and rhenium-188 complexes with one and two pendant bisphosphonate groups for imaging arterial calcification.
abstract: 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.
authors.affiliation: King's College London, Division of Imaging Sciences and Biomedical Engineering, St Thomas' Hospital, London SE1 7EH, UK. Philip.Blower@kcl.ac.uk.
authors.forename: Jayanta Kumar
authors.initials: JK
authors.lastname: Bordoloi
authors.forename: David
authors.initials: D
authors.lastname: Berry
authors.forename: Irfan Ullah
authors.initials: IU
authors.lastname: Khan
authors.forename: Kavitha
authors.initials: K
authors.lastname: Sunassee
authors.forename: Rafael Torres Martin
authors.initials: RT
authors.lastname: de Rosales
authors.forename: Catherine
authors.initials: C
authors.lastname: Shanahan
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Blower
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002114:Calcinosis / Q000000981:diagnostic imaging*; D004164:Diphosphonates / Q000737:chemistry*; D017886:Durapatite / Q000378:metabolism; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D008024:Ligands; D008297:Male; D008638:Mesenteric Arteries / Q000000981:diagnostic imaging; D015609:Organotechnetium Compounds / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D011868:Radioisotopes; D051381:Rats; D012211:Rhenium / Q000737:chemistry*; D013667:Technetium; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D001798:Blood Proteins; D004164:Diphosphonates; D006834:Hydrazines; D008024:Ligands; D015609:Organotechnetium Compounds; D011868:Radioisotopes; C010877:carbazic acid; D012211:Rhenium; D013667:Technetium; D017886:Durapatite