title: Synthesis, biological evaluation and molecular docking studies of high-affinity bone targeting N,N(') -bis (alendronate) diethylenetriamene-N,N'-triacetic acid: a bifunctional bone scintigraphy agent.
abstract: A bisphosphonate derivative DTPA-bis(alendronate) conjugate has been synthesized and evaluated as potential radiopharmaceutical for bone imaging. The compound was synthesized by the covalent coupling of DTPA-bis(anhydride) with alendronate and was char-acterized on the basis of IR, NMR and mass spectroscopy. It was labelled with (99m) Tc with 96% efficacy and was found stable for about 24 h under physiological conditions. Blood kinetic studies of (99m) Tc DTPA-bis(alendronate) showed a biexponential pattern as well as quick washout from the blood circulation. The biological t1/2 (F) and t1/2 (S) were found to be 50 min ± 0.001 and 6 h 30 min ± 0.005, respectively. Imaging and biodistribution studies showed a significant accumulation of (99m) Tc DTPA-bis(alendronate) conjugate at bone site. Bone-to-muscles ratios were 12.08 ± 0.001 at 1 h, 45.33 ± 0.001 at 4 h and 35.83 ± 0.001 at 24 h after post-injection, respectively. The receptor binding of the (99m) Tc-DTPA-bis (alendronate) was established on human bone cell line (Soas-2) revealed KD = 0.86 nm. The preliminary result of the (99m) Tc-DTPA-bis(alendronate) is encouraging to carrying out further in vivo experiment for targeted bone imaging because of good-bone-to-normal-organ contrast. Further docking analysis with molecular targets, farnesyl diphosphate synthase, geranylgeranyl pyrophosphate and osteocalcin revealed the high affinity of -17.419 and thus represents strong potential of bone-imaging agent.
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, Timarpur, Delhi, 110054, India; Department of Chemistry, University of Delhi, Delhi, 110007, India.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Chadha
authors.forename: Deepa
authors.initials: D
authors.lastname: Sinha
authors.forename: Anjani K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: Krishna
authors.initials: K
authors.lastname: Chuttani
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
mesh_terms: D000085:Acetates / Q000493:pharmacokinetics*; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects*; D002460:Cell Line; D006207:Half-Life; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D062105:Molecular Docking Simulation; D011817:Rabbits; D014018:Tissue Distribution
chemical_list: D000085:Acetates
keywords: alendronate; bone imaging; docking; radiopharmaceutical; spectroscopy