Organ distribution of fibrinogen-bound methotrexate in mice with Gardner lymphosarcoma.

The distribution of fibrinogen-bound 3H methotrexate was investigated in Gardner lymphosarcoma bearing mice. 3H labeled methotrexate (3H MTX) was covalently bound by means of aminopropyl carbodiimide to bovine and mouse fibrinogen (FBG). The preparations as well as the free 3H MTX were applied i.v. in a single dose to three groups of C3H mice on day 6 after the inoculation of Gardner lymphosarcoma. 3H MTX level was determined in the blood, spleen, tumor and liver. Sufficient amounts of MTX were released by proteolysis of FBG-MTX derivatives to induce chemotherapeutical effects. Protracted accumulation of MTX applied in the form of FBG-MTX derivatives was found in the spleen and in the liver, in contradistinction to free drug application, suggesting the proteolytic degradation as a directing step responsible for the prolonged persistence of FBG-MTX derivatives in the organs. In the tumor the highest amount of MTX was released from mouse FBG supporting the view of ready uptake of homologous FBG by tumors.