Biodistribution of HuCC49ΔCH2-β-galactosidase in colorectal cancer xenograft model

Yanke Yu, Lanyan Fang, Duxin Sun
2010 International Journal of Pharmaceutics  
Antibody-enzyme conjugate (AbE) has been widely studied for site-specific prodrug activation in tumors. The purpose of this study is to characterize the pharmacokinetics and tissue distribution of HuCC49ΔCH2-β-galactosidase conjugate. HuCC49ΔCH2 and β-galactosidase were chemically conjugated and injected into a LS 174T colon cancer xenograft model. A colorimetric assay was developed to quantify the HuCC49ΔCH2-β-galactosidase levels in plasma and tissues. The HuCC49ΔCH2-β-galactosidase conjugate
more » ... distributed into tumor tissue as early as 6 hours with the tumor/blood ratio of 5. This favored distribution of conjugate activity in the tumor tissue was maintained up to 4 days post conjugate injection, while the conjugate was cleared rapidly from blood and other normal tissues (heart, spleen, lung, liver, kidney and stomach). At a high dose of 3000 U/ kg, HuCC49ΔCH2-β-galactosidase conjugate saturated the antigen binding sites and yielded decreased tumor/normal tissue ratios compared to 1500 U/kg. These data suggest that HuCC49ΔCH2-β-galactosidase specifically target to the tumors to increase tumor selectivity.
doi:10.1016/j.ijpharm.2009.11.020 pmid:19944136 pmcid:PMC2815147 fatcat:s2fnfeqzkbagddt7bbjhgklp7a