[Kinetics of receptor-mediated radiotoxicity of 16alpha-[125I]-iodostradiol-3,17beta].
OBJECTIVE
The radiocytotoxic effects in estrogen receptor (ER) containing MCF-7 cells of a mamma carcinoma were investigated following incubation with [125I]E ranging from 1 h to 24 h.


METHODS
The receptor status of the cells was confirmed by immunohistochemical staining. The accumulation of [125I]E in MCF-7 cells was tested in the presence and absence of radioinert E and [127I]E and in ER-negative cells in comparison to ER-positive cells. The subcellular distribution was investigated in 0.25 M Saccharose by ultra centrifugation. The radiocytotoxicity was assessed in ER-positive and negative cells by a standard colony forming assay after incubating with [125I]E (1.85 kBq/ml-55.5 kBq/ml) for 1, 2, 4, 8, 12, and 24 h.


RESULTS
A significant cytotoxicity was observed 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.


CONCLUSIONS
The results suggest that the radioactivity was bound to ER. Through their nuclear localization radioestrogens tagged with radionuclides emitting very low energy electrons (Auger electrons) bear potential for therapy by ER-mediated deposition of lethal doses of ionizing radiation to single cells without affecting neighbouring cells. But, instead of 125I the shorter-living 123I shall be used for labelling because the deciding radiation effectes occur within the first 8 h.
Schomäcker
K
K
Klinik und Poliklinik für Nuklearmedizin, Universität zu Köln, Deutschland.
Fischer
T
T
Böttcher
B
B
Mraheel
S A
SA
Scharl
A
A
Gabruk-Szostak
B
B
Scheidhauer
K
K
Göhring
U J
UJ
Meller-Rehbein
B
B
Shukla
S K
SK
Schicha
H
H
D001692:Biological Transport; D001943:Breast Neoplasms; D002470:Cell Survival / Q000528:radiation effects*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D011960:Receptors, Estrogen / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D007457:Iodine Radioisotopes; D011960:Receptors, Estrogen; D004958:Estradiol; C024871:16 alpha-iodoestradiol
Die Kinetik von rezeptorvermittelter Radiotoxizität des 16 alpha-[125I]-Iodöstradiol-3,17 beta.