Targeted delivery of antineoplastic agent to bone: biodistribution studies of technetium-99m-labeled gem-bisphosphonate conjugate of methotrexate

Abstract

A methotrexate-bisphosphonate conjugate containing a peptide bond has been found to possess over five times greater antineoplastic activity against osteosarcoma in experimental animal models compared with methotrexate alone.

Methods: The conjugate was labeled with 99mTc in the presence of stannous ions to determine biologic distribution, with special reference to osseous tissue. Biodistribution studies were carried out in mice after intravenous administration of the labeled conjugate. Radionuclide imaging of rabbits was also performed.

Results: The labeled conjugate behaved like a bone-seeking agent.

Conclusion: The present study indicates that the concept of treating osteosarcoma or metastatic tumors of bone with this class of agents has a firm basis.