- Email: [email protected]
271 Growth inhibition of an adrenocortical carcinoma with aminogluthetimide
90s
269
NOVEL AROMATASE INHIBITORS AS IXYIBNTIALAGENTS FOR THE TRBATMEMT OF HoRVkXZDEPENDENT BREAST CANCER John Mann"
and Barbara Pietrzak, Chemistry Department, Reading University, Reading,UK.
A number of fluoro-steroidshave been prepared which have potent activity as inhibitors of placental aromatase. Their biological potency is compared with that of the known inhibitor 4-hydroxyandrost-4-e3,17-dione (4-m), both from in vitro studies and from in vivo studies using the MVU-induced mammary cancer in rats. Possible modes ofvity will be discussed.
270
Localisation of oestrogen sensitive tissues using lti-[1311]-iodo-17P-oestradiol with external scintigraphy. Elizabeth K. Symes, W.F. Coulson, P.J. 81, D.N. Hslphs & E.J.G. Milroy. The Middlesex Hospital Medical School, London, UK. Because of its high oestrogen receptor binding affinity l&X-iodo-oestradiolis selectivley accumulated by oestrogen sensitive tissues eg. uterus of rat. Suitably labelled with a gamma emitting isotope it is a potential agent for the localisation of soft tissue deposits of breast cancer in patients by external scintigraphy. We initially intended to label the compound with 1231 but due to the short t of # this isotope, its availability and the strictures of the chemical reaction (involving bromine/iodine exchange) its use is prohi:;;ively expensive. These disadvantages have been largely overcome by the use of I. 16@[1311]-oestradiol has been prepared at a specific activity of 3CX/mmol by a modification of Hochberg's published procedure and subsequent purification on Sepac silica gel cartridges. We are imaging patients with lo and known metastatic deposits at various times after the injection of _ 0.5 mCi. Time activity curve data will be shown discussing blood clearance, tissue uptake, liver and kidney clearance data. We will report on our results and their correlation with the oestrogen receptor status of the lo tmnour. To date one patient with a 1" tumour (receptor status pending) has been studied. Dp to 5h after injectfon no acccumulatfon was detected in the tunour. However, within lh the uterus could be imaged clearly.
271
GROWTH INHIBITION OF AN ADHENOCORTICAL CARCINOMA WITH AMINOGLUTHETIMIDE J. Weiss and H.J..SCHMOLL Abteilung hamatologie, Medizinische Hochschule Hannover, Federal Republic of Germany. Six months after surgery of an estrogen producing adrenocortical carcinoma with the symptoms of hypertonus, increasing body weight, gynecomastia and female hair type the 29 year old male patient had again increasing estrogen levels with tumor relapse in liver, lung and abdominal lymph nodes. 14 days after the beginning of treatment with aminogluthetimidethe elevated estrogen and lowered testosterone levels had normalized. The therapy was continued with a dosage of 12,5 mg/kg body weight daily per OS for 11 months. When the estrogen levels were increasing again the dosage was successively raised to 25 mg/kg. When substituting cortisolacetate and testosterone there were no severe side effects. Tumor volume has remained stationary now for 14 months. After one report from 1966 this is the second case of growth inhibition of a functioning adrenocortical carcinoma treated with aminogluthetimide alone. The normalization of hormone levels is explained by a block of aromatization of androgens to estrogens and several cytochrome P-450 mediated steroid hydroxylation steps, but the inhibition of tumor growth by aminogluthetimide still needs to be defined.
269
NOVEL AROMATASE INHIBITORS AS IXYIBNTIALAGENTS FOR THE TRBATMEMT OF HoRVkXZDEPENDENT BREAST CANCER John Mann"
and Barbara Pietrzak, Chemistry Department, Reading University, Reading,UK.
A number of fluoro-steroidshave been prepared which have potent activity as inhibitors of placental aromatase. Their biological potency is compared with that of the known inhibitor 4-hydroxyandrost-4-e3,17-dione (4-m), both from in vitro studies and from in vivo studies using the MVU-induced mammary cancer in rats. Possible modes ofvity will be discussed.
270
Localisation of oestrogen sensitive tissues using lti-[1311]-iodo-17P-oestradiol with external scintigraphy. Elizabeth K. Symes, W.F. Coulson, P.J. 81, D.N. Hslphs & E.J.G. Milroy. The Middlesex Hospital Medical School, London, UK. Because of its high oestrogen receptor binding affinity l&X-iodo-oestradiolis selectivley accumulated by oestrogen sensitive tissues eg. uterus of rat. Suitably labelled with a gamma emitting isotope it is a potential agent for the localisation of soft tissue deposits of breast cancer in patients by external scintigraphy. We initially intended to label the compound with 1231 but due to the short t of # this isotope, its availability and the strictures of the chemical reaction (involving bromine/iodine exchange) its use is prohi:;;ively expensive. These disadvantages have been largely overcome by the use of I. 16@[1311]-oestradiol has been prepared at a specific activity of 3CX/mmol by a modification of Hochberg's published procedure and subsequent purification on Sepac silica gel cartridges. We are imaging patients with lo and known metastatic deposits at various times after the injection of _ 0.5 mCi. Time activity curve data will be shown discussing blood clearance, tissue uptake, liver and kidney clearance data. We will report on our results and their correlation with the oestrogen receptor status of the lo tmnour. To date one patient with a 1" tumour (receptor status pending) has been studied. Dp to 5h after injectfon no acccumulatfon was detected in the tunour. However, within lh the uterus could be imaged clearly.
271
GROWTH INHIBITION OF AN ADHENOCORTICAL CARCINOMA WITH AMINOGLUTHETIMIDE J. Weiss and H.J..SCHMOLL Abteilung hamatologie, Medizinische Hochschule Hannover, Federal Republic of Germany. Six months after surgery of an estrogen producing adrenocortical carcinoma with the symptoms of hypertonus, increasing body weight, gynecomastia and female hair type the 29 year old male patient had again increasing estrogen levels with tumor relapse in liver, lung and abdominal lymph nodes. 14 days after the beginning of treatment with aminogluthetimidethe elevated estrogen and lowered testosterone levels had normalized. The therapy was continued with a dosage of 12,5 mg/kg body weight daily per OS for 11 months. When the estrogen levels were increasing again the dosage was successively raised to 25 mg/kg. When substituting cortisolacetate and testosterone there were no severe side effects. Tumor volume has remained stationary now for 14 months. After one report from 1966 this is the second case of growth inhibition of a functioning adrenocortical carcinoma treated with aminogluthetimide alone. The normalization of hormone levels is explained by a block of aromatization of androgens to estrogens and several cytochrome P-450 mediated steroid hydroxylation steps, but the inhibition of tumor growth by aminogluthetimide still needs to be defined.