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• W2316358366 abstract "A phosphonate derivative 10′-bis(acetamido)-ethane-bis[1,4,7-tri(methylene phosphonic acid)-1,4,7,10-tetraazacyclododecane] (DO3P-AME-DO3P), was synthesized with 90% yield in high purity. It was labeled with 99mTc in 97.5% efficiency and specific activity of 112−250 MBq/μmol. The binding affinity of 99mTc-DO3P-AME-DO3P towards bone minerals was tested in vitro by using hydroxy apatite as a bone model with absorption of 93% during the first hour of the experiment. Receptor binding assay on human bone cell line SAOS-2 demonstrated Kd value of 1.07 nM. Cell binding studies of DO3P-AME-DO3P on osteoblasts and osteoclasts cells performed in vitro displayed preferential affinity of the compound towards osteoclast (167.95 ± 3.56% dose/mg protein). The serum stability of 99mTc complex was found to be 96.8% after 24 h. Blood kinetics of 99mTc-DO3P-AME-DO3P performed on normal rabbits showed fast clearance with t1/2(F) = 15 min ± 0.014 min and t1/2(S) = 4 h 3 min ± 0.09 min. Biodistribution studies carried out in normal BALB/c mice showed bone-to-blood ratio of 20 and bone-to-muscle ratio of 33. The bone tissue demonstrated highest concentration of bound radioactivity with 10.73% ID/g at 1 h post injection. The protonation and stability constants were determined by pH-potentiometry titrations. The stability constants of DO3P-AME-DO3P with Lu(III), Sm(III), and Ho(III) were 19.7, 21.8, and 20.2 determined by “out of cell” method. The excellent bone seeking properties of DO3P-AME-DO3P make it a candidate of choice for SPECT imaging and preferential uptake of the compound in osteoclasts in comparison to osteoblasts; BMM and BMC can be used to understand the pathway of pathogenesis of osteoporosis and skeletal metastases." @default.
• W2316358366 created "2016-06-24" @default.
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• W2316358366 date "2011-01-11" @default.
• W2316358366 modified "2023-10-03" @default.
• W2316358366 title "Preclinical Evaluation of DO3P-AME-DO3P: A Polyazamacrocyclic Methylene Phosphonate for Diagnosis and Therapy of Skeletal Metastases" @default.
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• W2316358366 doi "https://doi.org/10.1021/bc100382c" @default.
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