Evaluation of ¹⁶¹Tb-Labeled Diphosphonates as Potential Bone-Targeting Agents.

Area of Science:

• Nuclear medicine and radiopharmaceutical chemistry.
• Development of targeted therapies for skeletal diseases.

Background:

• Bone metastases and skeletal diseases require effective bone-targeting agents.
• Diphosphonates are known for their bone-seeking properties.
• Terbium-161 (¹⁶¹Tb) is a promising radionuclide for targeted radionuclide therapy.

Purpose of the Study:

• To radiolabel etidronic acid (HEDP) and zoledronic acid (ZOL) with ¹⁶¹Tb.
• To evaluate the in vitro and in vivo properties of ¹⁶¹Tb-HEDP and ¹⁶¹Tb-ZOL as bone-targeting radiopharmaceuticals.
• To assess their potential for radionuclide therapy of bone metastases.

Main Methods:

• Radiolabeling of HEDP and ZOL with ¹⁶¹Tb at pH 7.
• In vitro stability studies in saline and human serum.
• Hydroxyapatite binding affinity and plasma protein binding assays.
• In vivo biodistribution studies in Wistar rats.
• Electrochemical analysis and Density Functional Theory (DFT) calculations.

Main Results:

• High radiolabeling yields (>98%) and excellent in vitro stability achieved for both complexes.
• ¹⁶¹Tb-HEDP and ¹⁶¹Tb-ZOL demonstrated strong hydroxyapatite binding, rapid blood clearance, and minimal soft tissue accumulation.
• ¹⁶¹Tb-ZOL showed lower renal and hepatic accumulation compared to ¹⁶¹Tb-HEDP, indicating higher safety and selectivity.
• Both complexes exhibited superior bone targeting compared to unchelated ¹⁶¹TbCl₃.
• DFT calculations confirmed ligand coordination and structural stabilization.

Conclusions:

• ¹⁶¹Tb-labeled HEDP and ZOL are stable, bone-targeting radiopharmaceuticals with favorable biodistribution profiles.
• These agents demonstrate potential for targeted radionuclide therapy of bone metastases and other skeletal diseases.
• Further investigation is warranted to explore their therapeutic efficacy.