Polyethylene glycol conjugates of methotrexate and melphalan: synthesis, radiolabeling and biologic studies

Polyethylene glycols (PEGs) are potential drug carriers for humanizing the therapeutic index of anti-cancer agents. In this paper, we report on the modification of the anticancer drugs, methotrexate (MTX) and melphalan (L-PAM), covalently linked to PEGs for drug delivery. Conjugates of MTX and L-PAM were analyzed through different spectroscopic techniques. Both conjugates were labeled with (99m)Tc by the classical way, using reducing agents at a physiologic pH. Blood kinetic data revealed the biphasic pattern of clearance. Evaluation of the in vitro cytotoxicity of the drug polymer conjugates on the U87MG human glioma cell line revealed that the conjugates showed enhanced dose-dependent cytotoxicity.