KINETIC OF RECEPTOR-MEDIATED RADIOTOXICIT Y OF 16-ALPHA-[I-125]-IODOESTRADIOL-3,17-BETA

Aim: The radiocytotoxic effects in estrogen receptor (ER) containing M CF-7 cells of a mamma carcinoma were investigated following incubation with [I-125]E ranging from 1 h to 24 h. Methods: The receptor status of the cells was confirmed by immunohistochemical staining. The accumu lation of [I-125]E in MCF-7 cells was tested in the presence and absen ce of radioinert E and [I-127]E and in ER-negative cells in comparison to ER-positive cells. The subcellular distribution was investigated i n 0.25 M Saccharose by ultra centrifugation. The radiocytotoxicity was assessed in ER-positive and negative cells by a standard colony formi ng assay after incubating with [I-125]E (1.85 kBq/ml-55.5 kBq/ml) for 1, 2, 4, 8, 12, and 24 h. Results: A significant cytotoxicity was obse rved only when ER-rich MCF-7-cells were incubated with [(125I)]E alone . The maximal cytotoxic effect was a reduction of survival fraction to 20-25%. This was achieved at radioactivity concentrations >37 kBq/ml. Maximal effect was seen after 8 h incubation, extension of incubation time did not further increase toxicity. Conclusion: The results sugge st that the radioactivity was bound to ER. Through their nuclear local ization radioestrogens tagged with radionuclides emitting very low ene rgy electrons (Auger electrons) bear potential for therapy by ER-media ted deposition of lethal doses of ionizing radiation to single cells w ithout affecting neighbouring cells. But, instead of I-125 the shorter -living I-123 shall be used for labelling because the deciding radiati on effectes occur within the first 8 h.