Preparation and biological study of 68Ga-DOTA-alendronate

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 (68Ga).Methods: DOTA-ALN was synthesized and characterized, followed by 68Ga-DOTA-ALN preparation, using DOTA-ALN and 68GaCl3 (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: 310-320GBq/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 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.

Keywords:

Ga-68 , DOTA , Alendronate , Biodistribution , Radiolabeling