The chemotherapy of C3H mice bearing Gardner lymphosarcoma with bovine fibrinogen-methotrexate derivative.

Derivative of bovine fibrinogen (FBG) containing chemically bound methotrexate (MTX) has been prepared by action of ethyldimethylaminopropyl carbodiimide. The derivative retained its solubility and clotability. Intraperitoneally administered FBG-MTX derivative one day after transplantation of the ascitic Gardner lymphosarcoma prolonged distinctly the survival of C3H mice. The intravenous application of FBG-MTX derivative to mice bearing the solid form of the tumor exerted chemotherapeutic effect resulting in prolongation of survival. The local application of FBG-MTX solutions followed by injection of thrombin resulted in the formation of a fibrin clot in the tumor area which persisted at least 48 hours. Local chemotherapy of the solid tumor with fibrin clot containing MTX performed on day 1 or 3 led to significant prolongation of survival of the treated animals. Mechanism of MTX liberation and the possible application of FBG-MTX derivative in chemotherapy of tumors are discussed.