In a previous study, we showed that targeted delivery of bovine liver
catalase to hepatocytes by direct galactosylation augmented the inhibitory effect of the
enzyme on experimental hepatic
metastasis of colon
carcinoma cells (unpublished data). Here, we examined the ability of
catalase to inhibit
tumor metastasis to the lung by controlling its biodistribution. Four types of
catalase derivative, Gal-CAT, Man-CAT, Suc-CAT and
PEG-CAT, were synthesized. Experimental pulmonary
metastasis was induced in mice by i.v. injection of 1 x 10(5) colon 26
tumor cells. An i.v. injection of
catalase (35,000 units/kg) partially, but significantly, decreased the number of colonies in the lung 2 weeks after
tumor injection, from 93 +/- 29 (saline injection) to 63 +/- 23 (p < 0.01). Suc-CAT, Man-CAT and Gal-CAT showed effects similar to those of
catalase on the number of colonies. However,
PEG-CAT greatly inhibited pulmonary
metastasis to 22 +/- 11 (p < 0.001). Furthermore, s.c. injection of
catalase also greatly inhibited
metastasis (11 +/- 6, p < 0.001). Neither inactivated
catalase nor BSA showed any effects on the number of metastatic colonies, indicating that the enzymatic activity of
catalase to detoxify H(2)O(2) is the critical factor inhibiting
metastasis. (111)In-PEG-CAT showed a sustained concentration in plasma, whereas s.c.-injected (111)In-catalase was slowly absorbed from the injection site. These results suggest that retention of
catalase activity in the circulation is a promising approach to inhibit pulmonary
metastasis.