title: Preparation and Biological Study of (68)Ga-DOTA-alendronate.
abstract: OBJECTIVE
  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)GaCl3 (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 log P 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Tehran University of Medical Sciences, Faculty of Pharmacy, Tehran, Iran.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Fakhari
authors.affiliation: Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran.
authors.forename: Amir R
authors.initials: AR
authors.lastname: Jalilian
authors.affiliation: Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Johari-Daha
authors.affiliation: Tehran University of Medical Sciences, Faculty of Pharmacy, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Shafiee-Ardestani
authors.affiliation: Tehran University of Medical Sciences, Faculty of Pharmacy, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Khalaj
keywords: Alendronate; Biodistribution; DOTA; Ga-68; Radiolabeling