Radiosynthesis and Animal Studies of 111In-DTPA-bis-alendronate Complex

Abstract

Purpose- In order to develop new bone imaging agent based on bisphosphonate moiety, an alendronate based complex was designed and prepared in this study. Methods- A DTPA-conjugated bis-alendronate analog (DTPA-bis-ALN) 3, was prepared for possible bone imaging after radiolabeling with 111In. Radiolabeled DTPA-bis-ALN complex was prepared starting radionuclide in chloride form and DTPA-bis-ALN in 30-90 min at 50-60°C in acetate buffer followed by solid phase purification on C18 Sep-Pak cartridge. RTLC was used for radiochemical purity determination followed by log P determination, stability studies, hydroxyl apatite tests and biodistribution studies in normal rats and imaging. Results- Specific activity 1.1-1.3 TBq/mmmol was obtained for 111In-complex. The log Ps was calculated 0.48 for the complex consistent with water soluble complexes followed by stability test. The biodistribution of the labeled compound in normalrats demonstrated activity uptake in kidneys. Conclusions- The anionic property of poly-dentate complex led to renal excretion instead of bone accumulation. These data showed that the developed complexes are not suitable agents for bone imaging as expected.

Keywords

• Alendronate
• In-111
• Biodistribution
• DTPA-conjugate
• Imaging.