Preparation and biological studies of 68Ga-DOTA-alendronate

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).
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.
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 ( 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.