Targeted delivery of antineoplastic agent to bone: biodistribution studies of technetium-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 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.


CONCLUSIONS
The present study indicates that the concept of treating osteosarcoma or metastatic tumors of bone with this class of agents has a firm basis.
Department of Nuclear Medicine, University of Connecticut Health Center, Farmington 06030, USA.
F
F
Hosain
R P
RP
Spencer
H M
HM
Couthon
G L
GL
Sturtz
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy*; D001842:Bone and Bones / Q000000981:diagnostic imaging; D004164:Diphosphonates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D012516:Osteosarcoma / Q000188:drug therapy*; D011817:Rabbits; D011877:Radionuclide Imaging; D013670:Sodium Pertechnetate Tc 99m; D014018:Tissue Distribution
D000964:Antimetabolites, Antineoplastic; D004164:Diphosphonates; C097566:methotrexate bisphosphonate; D013670:Sodium Pertechnetate Tc 99m; D008727:Methotrexate