# BIOLOGICALLY ACTIVE STEROID ANALOGS

> **NIH NIH R01** · YALE UNIVERSITY · 1989 · $237,736

## Abstract

This laboratory synthesized the first biologically active gamma-
emitting steroid with the requisite characteristics for a steroid
receptor ligand.  This steroid, an estrogen, 16alpha-iodoestradiol
(16alpha-IE2) is extremely stable and binds to the estrogen
receptor with high affinity.  Because it can be synthesized
carrier-free, 2,200 Ci/mmol, it is widely used for the sensitive
analysis of the estrogen receptor.  Recently we have synthesized
an analog of this iodinated C18-steroid, 11beta-methoxy-16alpha-
iodoestradiol (11beta-CH3O-16alphaIE2) which is also an excellent
ligand for the estrogen receptor, but unlike 16alpha-IE2, the
11beta-methoxy analog also has excellent estrogenic properties in
vivo.  This steroid is an extremely potent estrogen, and when
labelled with radioiodine it concentrates in estrogen target tissues
in high levels and for prolonged periods.  Furthermore, the
11beta-methoxy analog produces extremely high levels of
radioactivity in the target tissues relative to all other tissues.
These characteristics make 11beta-CH3-16alpha-IE2 a unique
probe of the estrogen receptor, and we will synthesize this
11beta-methoxy analog labelled with 2-123I and 125I and use the
radiotracers to study estrogen responsive tissue.  We intend to
synthesize 11beta-CH3O-16alpha-123EI2 as a receptor based
imaging agent for the detection and monitoring of estrogen
receptor containing tumors.  The 123I-labelled estrogen will be
characterized for estrogen receptor binding in vitro; target tissue
uptake in vivo.  We will administer 11beta-CH3O-123IE2 to
patients with breast and endometrial cancer in order to image
their cancer and metastases with a gamma-camera.  After
surgery, the estrogen receptor content of the tumors will be
quantified to demonstrate that the in vivo detection of this tracer
correlates with estrogen receptor content of the tumor.  In
addition, we will utilize this unique ligand labelled with 125I to
investigate other aspects of estrogen action, such as the
autordiographic study of estrogen receptor containing regions of
the brain, and the specific cytotoxic destruction of estrogen
sensitive cells and genes.  We will continue the design and
synthesis of specific probes of other hormone receptors, including:
characterization of the biological activity and the specific binding
of two 125I-ligands we have recently synthesized for the
progesterone receptor, one of which is also a photoaffinity label;
the synthesis of 125I-ligands for the glucocorticoid and androgen
receptors, as well as, biotinylated and fluorescent ligands for the
glucocorticoid and estrogen receptors.  We are synthesizing and
testing a series of metabolically labile estrogens.  These
compounds bind to the estrogen receptor with high affinity, and
are estrogenically active when tested directly.  But because they
are biologically labile, they are rapidly enzymatically converted
into estrogenically inactive metabolites.  Consequently, these
estrogens appear to be system...

## Key facts

- **NIH application ID:** 3175644
- **Project number:** 5R01CA037799-06
- **Recipient organization:** YALE UNIVERSITY
- **SAM.gov UEI:** FL6GV84CKN57
- **Principal Investigator:** RICHARD B HOCHBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $237,736
- **Award type:** 5
- **Project period:** 1984-08-01 → 1991-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175644

## Citation

> US National Institutes of Health, RePORTER application 3175644, BIOLOGICALLY ACTIVE STEROID ANALOGS (5R01CA037799-06). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3175644. Licensed CC0.

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