Preparation and biological studies of ^68Ga-DOTA-alendronate

Objective(s): In line with previous research on the development of conjugated bisphosphonate ligands as new boneavid agents, in this study, DOTA conjugated alendronate (DOTAALN) was synthesized and evaluated after labeling with gallium68 (68Ga).Methods: DOTAALN was synthesized and characterized, followed by 68GaDOTAALN preparation, using DOTAALN and 68GaCl3 (pH: 45) at 9295°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 thinlayer chromatography; specific activity: 310320GBq/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 afterthe injection. The data were also confirmed by sequential imaging at 3090 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.