Radiolabelling and biological apprisal of ??mtechnetium labeled tamoxifen for anticancer activity

Abstract

The aim of the present study was to develop the procedure for radiolabeling of an anticancer drug tamoxifen with 99mTc for tumor diagnosis and to evaluate the antitumor effect of tamoxifen in EAC bearing mice. The Ehrlich ascites carcinoma (EAC) cells were injected invivo in Balb-C mice by intraperitoneal (i.p.) inoculation of 2x106 cells/mice after every 10 days. The study included the radiolabeling of tamoxifen, in vitro stability of radiolabeled drug, invitro binding of radiolabeled drug with plasma protein, partition coefficient and biodistribution of radiolabeled drug in mice. MTT assay, mean survival time and % increase in life span, body weight, tumor size, volume and hematological parameters (Red blood cells, Haemoglobin, Haematocrit, Mean corpuscular haemglobin (MCH), Mean cellular heamoglobin concentration, Platelets, Lymphocytes, Monocytes, Eosinophils, Granulocytes and Red cell distribution width) were also evaluated. Radiolabeling of tamoxifen with technetium-99m (99mTc) was 97%. Invitro stability of the labeled complex was increased with time and found maximum at 2 hours (98.1.± 0.17). Partition coefficient of the labeled drug showed that it was highly lipophilic. Biodistribution study in tumor bearing mice exhibited high uptake in tumor cells. Tamoxifen significantly increased the life span and mean survival time of tumor bearing mice and significantly reduces the tumor weight, size and volume, body weight as compared to the control (EAC bearing) group. In conclusion, the present study indicates that 99mTc labeled tamoxifen is a potentially strong tumor diagnostic agent with low uptake in normal tissues and has anticancer activity in solid tumors.