Lymphotropic accumulation of an antitumor antibiotic protein, neocarzinostatin

Abstract

In vivo distribution of the antitumor antibiotic neocarzinostatin (NCS) at about the clinical dose level, based on bioactivity, was studied in rats, in the presence of proteolytic inhibitors preventing degradation of NCS during the bioassay. The activity of NCS was found to accumulate to a much larger extent in the lymph nodes, especially popliteal, axillary and lumbar lymph nodes, than in other organs except the bladder, after intravenous (i.v.) injection. In addition, accumulation in regional lymph nodes was found to be very high after subcutaneous (s.c.) injection. Bioactivity of NCS was detected also in other organs and tissues such as the kidney, bone marrow, blood, lung, small intestine, liver and spleen, but it was lower than expected. In the heart, stomach, large intestine, muscle and prostate, activity of NCS was not detected. Excretion of NCS in urine 10 min after an i.v. injection was about 80 times more than that after an s.c. injection. Urinary recovery of NCS was almost completed in 90 min, which yielded 44 and 12% of the total i.v. and s.c. dosage, respectively. The present findings of the highly lymphotropic nature of NCS recommends its application for control of the lymphatic metastasis in man.