ABSTRACT
Objective[s]: In line with previous research on the development of conjugated bisphosphonate ligands as new bone-avid agents, in this study, DOTA-conjugated alendronate [DOTA-ALN] was synthesized and evaluated after labeling with gallium-68 [[68]Ga]
Methods: DOTA-ALN was synthesized and characterized, followed by [68]Ga-DOTA-ALN preparation, using DOTA-ALN and [68]GaCl[3] [pH: 4-5] at 92-95°C for 10 min. Stability tests, hydroxyapatite assay, partition coefficient calculation, biodistribution studies, and imaging were performed on the developed agent in normal rats
Results: The complex was prepared with high radiochemical purity [>99% as depicted by radio thin-layer chromatography; specific activity: 310-320 GBq/mmol] after solid phase purification and was stabilized for up to 90 min with a logP value of -2.91. Maximum ligand binding [65%] was observed in the presence of 50 mg of hydroxyapatite; a major portion of the activity was excreted through the kidneys. With the exception of excretory organs, gastrointestinal tract organs, including the liver, intestine, and colon, showed significant uptake; however, the bone uptake was low [<1%] at 30 min after the injection. The data were also confirmed by sequential imaging at 30-90 min following the intravenous injection
Conclusion: The high solubility and anionic properties of the complex led to major renal excretion and low hydroxyapatite uptake; therefore, the complex failed to demonstrate bone imaging behaviors