Therapy of estrogen receptor-positive micrometastases in the peritoneal cavity with Auger electron-emitting estrogens--theoretical and practical considerations.
Previous studies have demonstrated that Auger electron-emitting estrogens, when associated with the estrogen receptor (ER), can effect breaks in DNA and ER-dependent radiotoxicity. To evaluate the potential of [123I]-iodoestrogens, ([123I]-IE) to treat ER-positive human cancer cells, we have studied the effect of incubation of [123I]-IE with ER-positive MCF-7 breast cancer cells on cell survival in vitro and found that subnanomolar concentrations of [123I]-IE effectively reduce survival, with a mean lethal dose of about 800 decays per cell. MCF-7 cells incubated 30 min with 2 nM [123I]-IE (13 MBq/ml) showed a 2 log reduction in the ability to form tumors in immunodeficient mice. Evaluation of a mathematical model for [123I]-IE therapy for intraperitoneal micrometases in vivo in the mouse, based on variables related to the (a) specific activity of [123I]-IE; (b) its affinity for ER; (c) the characteristics of the uptake and retention of [123I]-IE by the target cells; (d) the concentration of ER in the tumor cells and (e) the tumor weight suggest that such therapy may be feasible.
DeSombre
E R
ER
Ben May Institute for Cancer Research, The University of Chicago, IL, USA. gdesombr@ben-may.bsd.uchicago.edu
Hughes
A
A
Hanson
R N
RN
Kearney
T
T
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002470:Cell Survival; D004583:Electrons / Q000627:therapeutic use*; D004967:Estrogens / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics* / Q000494:pharmacology; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D010534:Peritoneal Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D011960:Receptors, Estrogen / Q000502:physiology
D004967:Estrogens; D018796:Immunoconjugates; D007457:Iodine Radioisotopes; D011960:Receptors, Estrogen