TARGETED DELIVERY OF ANTINEOPLASTIC AGENT TO BONE - BIODISTRIBUTION STUDIES OF TC-99M-LABELED GEM-BISPHOSPHONATE CONJUGATE OF METHOTREXATE

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 metho trexate alone. Methods: The conjugate was labeled with Tc-99m in the p resence of stannous ions to determine biologic distribution, with spec ial 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 labe led conjugate behaved like a bone-seeking agent. Conclusion: The prese nt study indicates that the concept of treating osteosarcoma or metast atic tumors of bone with this class of agents has a firm basis.