Disposition of methylglyoxal bis(guanylhydrazone) (MGBG, NSC-32946) in man

A high-pressure liquid chromatographic method was utilized to determine the concentration of the antileukemic agent methylgloxal bis(guanylhydrazone) (MGBG, NSC-32946) in tissue samples obtained at autopsy from patients who received MGBG. In a patient with cholangiocarcinoma who received one course of MGBG (500 mg/m2), the highest drug concentration was found in normal liver tissue. However, the drug concentration in intrahepatic tumor tissue was only 10% of that found in uninvolved liver. In a patient with acute myelogenous leukemia (AML) who received 12 courses of MGBG therapy, highly infiltrated lymph node tissue was found to contain the highest concentration of MGBG. High concentrations of the drug were also found in liver, spleen, kidney, adrenal, and thyroid. The drug penetrated well into normal brain tissue. After repeated administration, high drug concentrations were found in cerebral and cerebellar gray matter. These studies suggest that there is no selective uptake of MGBG into solid tumors early after drug administration and provide a pharmacologic rationale for testing this agent against endocrine and intracerebral tumors in man.