GALLIUM-67 DISTRIBUTION AND WHOLE BODY RETENTION IN METHOTREXATE TREATED RATS
Abstract
Gallium-67 citrate is a radiopharmaceutical which localizes in tumors, abscesses, and inflammatory lesions. Gallium-67 is used to stage Hodgkin's disease and to follow the course of various neoplastic diseases in patients being treated with chemotherapeutic agents. It is believed that the iron-binding protein transferrin is required for the transport of gallium-67 to the site of localization. Methotrexate is an antimetabolite type cancer chemotherapeutic agent that is hepatotoxic. Since transferrin is synthesized primarily in the liver and treatment with methotrexate may be hepatotoxic, an alteration in the distribution and whole body retention of gallium-67 may occur from chronic treatment with methotrexate. The purpose of this investigation was to examine the biodistribution and whole body retention of gallium-67 in rats which had been treated for up to three weeks with methotrexate. Methotrexate was administered intraperitoneally at a dose of 250 (mu)g/kg per day for five days each week. The influence of methotrexate on the unbound iron-binding capacity and the total iron-binding capacity of transferrin and serum iron was examined, also. Small decreases in gallium-67 levels were observed in blood, spleen, and muscle of drug treated animals in relation to normal saline controls. Although small in magnitude, gallium-67 whole body elimination was more rapid in drug treated animals than controls after two or three weeks of methotrexate treatment. The study showed no effect of methotrexate treatment on the unbound iron-binding capacity or total iron-binding capacity of transferrin or serum iron. The results of the investigation infer that alterations in the biodistribution and retention of gallium-67 from methotrexate treatment may not be of clinical significance.
Degree
Ph.D.
Subject Area
Pharmaceuticals
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