Seocalcitol (
EB 1089) is under development for the treatment of hepato-cellular
carcinoma (HCC). The tissue distribution of 3H-seocalcitol was investigated in comparison to 3H-calcitriol in rats. Quantitative whole-body autoradiography was used to quantify the tissue distribution. The greatest difference in distribution between the two compounds was observed in the bloodstream. For most tissues the ratio
seocalcitol/
calcitriol varied between 0.2 and 3.1. The concentration of radioactivity in the liver was almost the same for the two compounds. For
seocalcitol the concentration in the liver was 10 times higher than in serum. Assuming that the liver/serum concentration ratio is the same in rats and humans, the concentration of
seocalcitol in the human liver is expected to be higher than the concentration resulting in more than 50% inhibition of
cancer cell proliferation, and thus pharmacologically effective in HCC. It is questionable whether
calcitriol would be present in the human liver in sufficient concentrations to be effective for the treatment of HCC, as the antiproliferative activity of
calcitriol is generally more than 10-fold lower compared to that of
seocalcitol and as
calcitriol can only be administered at a dose that is ca. three-fold lower than the dose of
seocalcitol.