Introduction Vascular calcification is considered to be a significant predictor of coronary heart disease. It is also associated with serious clinical complications such as left ventricular hypertrophy and calcific uremic arteriolopathy. Matrix vesicles and apoptotic bodies (AB’s) released by calcifying vascular smooth muscle cells (VSMC’s) form the nidus for calcification in the vessel wall. Electron beam computed tomography (EBCT), the gold standard for non-invasive imaging and quantitation of vascular calcification fails to provide any information at the molecular and cellular level. It cannot differentiate between intimal and medial calcification and the early phase of calcification is not revealed on computed tomography (CT) images. We have synthesised a series of novel bone-seeking complexes of 99mTc and used them for the detection of the process of vascular calcification in rat models.
Materials and method Two established bone seeking radiopharmaceutical 18F-Fluoride and 99mTc-Methylenediphosphonate (MDP), as well as two novel bisphosphonates, 99mTc(CO)3-Dipicolylamine (DPA) Alendronate and 99mTc-Nitrido Bis(dithiocarbamatebisphosphonate) [99mTc-N(DTC-BP)2] were used in the study. In-vitro binding measurement studies were performed to compare the binding efficiencies of the radiopharmaceuticals with minerals from intimal and medial calcifications, powdered equine bone, synthetic hydroxyapatite and AB’s isolated from calcifying VSMC’s. In-vivo imaging was performed on Sprague-Dawley (S-D) rats fed with a warfarin diet to induce calcification in the tunica-media. SPECT-CT and PET-CT scanning were done on week 1, 2 and 4 of the diet to monitor progression of disease.
Results The in vitro binding efficiencies of radiopharmaceuticals to the minerals were ranked as:
Medial Mineral: 99mTc-DPA Ale >99mTc-N(DTC-BP)2 >18F-Fluoride >99mTc-MDP.
Intimal mineral: 99mTc-DPA Ale >18F-Fluoride >99mTc-N(DTC-BP)2 >99mTc-MDP.
In-vivo imaging with SPECT-CT and PET-CT revealed uptake of radiotracers in the aorta of warfarin fat rats as early as week 1 of the diet, where as calcification on the CT images was observed on week 4 in the same animal.
Conclusions The findings indicate that novel bone seeking radiopharmaceuticals can bind with minerals present in intimal and medial aortic calcification and AB’s released by calcifying VSMC’s. In-vivo imaging results show that SPECT and PET scanning with bone seeking radiotracers can detect the process of calcification earlier than CT.
- vascular calcification
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