期刊
DALTON TRANSACTIONS
卷 44, 期 11, 页码 4963-4975出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4dt02965h
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资金
- Centre of Excellence in Medical Engineering - Wellcome Trust
- EPSRC [WT088641/Z/09/Z]
- Kings College London
- UCL Comprehensive Cancer Imaging Centre - CRUK
- EPSRC
- MRC (England)
- DoH (England)
- British Heart Foundation centre of Research Excellence at King's College London
- National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's
- St Thomas' NHS Foundation Trust
- King's College London
- Wellcome Trust
- Higher Education Commission (HEC), Islamabad, Pakistan
- British Heart Foundation [RG/11/14/29056] Funding Source: researchfish
- Cancer Research UK [16463] Funding Source: researchfish
The first Tc-99m and Re-188 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 Tc-99 and stable rhenium analogues as uncharged, mononuclear nitridobis(dithiocarbamate) complexes was determined by electrospray mass spectrometry. The Tc-99m 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 Tc-99m-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 Tc-99m-MDP agent in which the bisphosphonate group is bound directly to Tc. The Re-188 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.
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