This collaborative investigation is to study steroid hormone receptor biology in ovarian and endometrial tumors. The coordinated program will evaluate the use of radioactive ligands to image and/or treat receptor-rich malignancies and will explore the protein products that result from hormone-receptor interaction as possible aids in the diagnosis of neoplasms. The specific aims of each of the component projects are:

1. To identify differences in protein synthesis and in estrogen and progestin receptor protein in normal and neoplastic endometrium and related stromal epithelial interactions to understand their nature and regulation. To establish the feasibility of using radiolabeled ligands in humans by studying their receptor affinity and biology in culture and experimental animals.

2. To identify and characterize cellular responses to the estrogen-ER stimulus in normal and neoplastic ovarian ER-rich cells and the effect of Auger electron emissions from ER ligands on target cell functions. Imaging pharmacokinetic in vivo studies will be performed.

3. To develop immunohistologic and immunoelectron microscopic techniques, identifying estrogen and progesterone receptors for characterization of their cellular/subcellular distribution in tissues and cells. To compare immunocytochemical assays with steroid-binding assays of receptors in ovarian and endometrial carcinomas.

4. To synthesize estrogenic and anti-estrogenic radiopharmaceuticals labeled with Auger electron emitting and//or gamma ray emitting isotopes. To collaborate in the evaluation of their utilities and hazards and to determine the potential of these radiopharmaceuticals in therapy and imaging in endometrial and ovarian carcinomas.

5. To conduct human pilot studies to evaluate radiolabeled ligands for imaging and/or therapy of receptor containing tumors.

6. To coordinate the program and provide accurate and timely distribution of tissues for research; to provide for systematic collation and evaluation of experimental results and research planning.

P01CA027476

1980-04-01

1989-07-31