Synthesis and assessment of 99mTc chelate-conjugated alendronate for development of specific radiopharmaceuticals.
Indole-based alendronate (AI) was derived from the condensation reaction of indole 3-carboxaldehyde with sodium alendronate (ALN) and was characterized by various spectroscopic methods (e.g., ultraviolet, fourier-transform-infrared, and liquid chromatography mass spectrometry). The AI was labeled with (99m)Tc and radiochemical purity was above 97%, which was ascertained by instant thin-layer chromatography, using different solvent conditions, with a specific activity 2-5 mCi/mg. The receptor ligand assay on human bone cell line Soas-2 showed K(D) = 0.55 nM. The derivative (AI) was stable, which was determined under physiologic conditions up to 24 hours The blood kinetic study showed a biexponential pattern as well as quick wash-out from the circulation with varying biologic t(1/2)(F) and t(1/2)(S). Excellent-quality radio images were recorded of bone, showing a rapid clearance of background activity, at an early visualization at 1.5 hours. The excretory pathway of the derivative was through the kidneys, which was evidenced by biodistribution studies. Thus, the newly synthesized derivative can be considered as a specific bone-seeking agent.
Shukla
Gauri
G
Department of Cyclotron and Radiopharmaceutical Sciences, INMAS, Delhi, India.
Tiwari
Anjani K
AK
Sinha
Deepa
D
Srivastava
Rakesh
R
Cahndra
Hairsh
H
Mishra
Anil K
AK
D019386:Alendronate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D007211:Indoles / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013055:Spectrophotometry, Infrared; D013667:Technetium / Q000737:chemistry*; D014018:Tissue Distribution
D007211:Indoles; D019275:Radiopharmaceuticals; D013667:Technetium; C012381:indole-3-carbaldehyde; D019386:Alendronate