Images of estrogen-receptor-positive breast tumors produced by estradiol labeled with iodine I 123 at 16 alpha.

OBJECTIVE: To examine the suitability of estradiol labeled with iodine I 123 at 16 alpha for imaging estrogen-receptor-positive breast carcinoma using imaging instrumentation that is widely available. DESIGN: Single-photon emission computed tomographic imaging survey of 29 women with suspected primary or expected recurrent breast carcinoma. SETTING: University-based referral center. PARTICIPANTS: Twenty-nine women undergoing diagnosis for primary or recurrent breast carcinoma. Selection was voluntary. MAIN OUTCOME MEASURE: Qualitative imaging study designed to provide tomographic data of radioligand retention and descriptive data of imaging results. RESULTS: Single-photon emission computed tomographic imaging using 123I-estradiol at 16 alpha was performed for patients with breast carcinoma. Independent readers, without knowledge of receptor status or proven disease, interpreted the films. Scintigraphic detection was most noteworthy in patients with chest wall tumors and inflammatory breast cancer. Agreement between readers was 98% for true-negative readings and 94% for true-positive readings, but only 60% for false-positive and false-negative film readings. CONCLUSIONS: Our results indicated that areas shown on imaging were also found to have estrogen-receptor activity and that radioligand accumulation can occur with low frequency in some surgically explored tissue. Radioligand imaging with 16 alpha-123I-estradiol can locate estrogen-receptor-positive breast tumors, including some that may be difficult to detect using conventional diagnostic imaging.

Prolonged clearance of intraperitoneal 16 alpha-[125I]iodo-17 beta-estradiol in presence of ascites.

Radioestrogens have potential as adjunct therapeutic agents against ovarian carcinoma, because selected radionuclides can deposit lethal doses of radiation to tumor cells and many ovarian carcinomas and their metastases express estrogen receptors. Because intraperitoneal administration is a possible approach, we investigated absorption from the peritoneal cavity of a radioiodoestradiol after intraperitoneal application in rats with and without ovarian tumors and ascites and compared the distribution of the radioactivity with that obtained after intravenous injection. In the absence of ascites, 70% of the intraperitoneal dose was cleared into the intestine within 2 hours after injection, indicating fast absorption from the peritoneal cavity. In the presence of ascites, clearance of intraperitoneal radioiodoestradiol was considerably slower; at 2 hours after injection, 50% of the injected dose remained in the ascites, mostly as radioiodoestradiol. Uptake of radioactivity in estrogen receptor-rich tissues, e.g., uterus, after intraperitoneal injection was high (about 20:1 over blood), regardless of the presence of ascites, but moderately lower than that observed after intravenous injection of radioiodoestradiol.

Characterization of high specific activity [16 alpha-123I]Iodo-17 beta-estradiol as an estrogen receptor-specific radioligand capable of imaging estrogen receptor-positive tumors.

16 alpha-[123I]Iodo-17 beta-estradiol (16 alpha-[123I]E2) has been characterized for use as a selective radioligand for estrogen receptor (ERc) that is capable of generating in situ images of ERc-positive tumors. High specific activity 16 alpha-[123I]E2 (7,500-10,000 Ci/mmol) was used in all determinations. Radiochemical purity was determined by thin layer chromatography, and the selectivity of radioligand for ERc was evaluated using size exclusion high performance liquid chromatography on ERc prepared from rodent uteri. Efficiencies of radioidination approaching 100% were achieved, and excellent receptor selectivity was obtained even when the efficiency of radioiodination was as low as 10%. Low radiochemical purity was always associated with poor selectivity for ERc. No new radioligand species was generated during the course of radiodecay; however, reduced binding over time, even when increased activity was used to compensate for radiodecay, indicated that the formation of a radioinert competitor does occur. 16 alpha-[123I]E2 demonstrated stable, high affinity binding to ERc and was concentrated by ERc-positive tissues. After injecting 16 alpha-[123I]E2 in vivo, images of ERc-containing tissues were obtained, including rabbit reproductive tract and dimethylbenzanthracene-induced tumors. The demonstrations of ERc selectivity and image formation both indicate that 16 alpha-[123I]E2 should have promise as a useful new radiopharmaceutical for imaging ERc-positive cancers.

The biodistribution of Br-77-labeled estrone: visualization of tissues containing increased estrogen receptors.

The biodistribution of a lipid-soluble brominated female sex hormone, Br-77-labeled estrone, has been determined in dogs and rabbits. Following i.v. or intragastric administration, Br-77-labeled estrone localized in the gallbladder bile within 20-25 min. Fifty-six percent of the injected activity was found in the bile at 90 min. Breast tissue was imaged by scintillation camera in three female dogs with postpartum breast enlargement at 24 hr following i.v. injection. Analysis of digitized images revealed 50% more counts per pixel in stimulated female breast tissue than was in surrounding tissue. Increased Br-77 activity in the breast was associated with the presence of increased concentrations of estrogen receptors.

In vitro ovulation from adult hamster ovary.

The purpose of the study was to achieve in vitro ovulation in order to acquire corpora lutea in vitro at "time zero" of their formation. Such in vitro corpora lutea would later be the subject of studies on maintenance and lysis of corpora lutea in vitro. Ovaries from adult hamsters, explained into chemically defined medium between 23:00 hours on the day of proestrus and 01:00 hours on the day of estrus, were examined in the culture medium at 10:00 hours on the day of estrus i.e., after 9 to 12 hours of incubation. Ovulated follicles (young corpora lutea) of differing stages of corpus luteum formation were observed in some of the explants, but not at all. Almost all ovulated ova, surrounded by their cumuli oophori, remained adherent to the area of rupture when the incubation was ended. In vitro ovulation occurs in chemically defined medium without added hormones. It is possible to obtain corpora lutea in vitro at "time zero" of their formation.