Diethylstilbestrol (DES) labeled with Auger emitters: potential radiopharmaceutical for therapy of estrogen receptor-positive tumors and their metastases?

Fischer, Thomas; Schomacker, Klaus; Schicha, Harald

PURPOSE Diethylstilbestrol (DES) is a well-known, non-steroidal estrogen with high affinity to the estrogen receptor (ER). Labeled DES would be a useful tool for therapy of ER-positive mammary carcinomas and their metastases. Particularly with Auger emitters, high cytotoxic potential combined with only slight side effects can be expected. MATERIALS AND METHODS DES was labeled by a new method with higher yield and specific activity than former methods. Cytotoxic effects on MCF-7 (human, Caucasian, breast, adenocarcinoma) cells, were tested in relation to radioactivity concentration applied and location of decay. Different iodine isotopes ((123)I, (125)I, (131)I) bound to DES or in the form of iodide were compared with regard to induction of intracellular DNA (deoxyribonucleic acid) fragmentation, and decrease of viability. For this purpose the 'Cell Death Detection Enzyme-Linked ImmunoSorbent Assay (ELISA)' and the water soluble tetrazolium salt WST-1 were used. The radiation protective effects of the radical scavenger vitamin C were also tested. RESULTS The experiments showed a significantly lower viability of cells exposed to the Auger emitters than those with the beta-emitter (131)I. All nuclides induced intracellular DNA fragments. The maximum amount of intracellular DNA fragments was different for all nuclides: (131)I-DES <(125)I-DES <(123)I-DES. With isotopes in the form of iodide, no increase of intracellular DNA fragmentation could be detected. Vitamin C reduced intracellular DNA fragmentation significantly, which points to an induction mechanism mainly via free radicals. CONCLUSIONS Labeled DES is a promising compound with high cytotoxic potential for treatment of ER-positive mamma carcinomas and their metastases.