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INV-13041
Background
Breast cancer has become the most common cancer globally as of 2021, accounting for 12% of all new annual cancer cases worldwide, according to the World Health Organization. Among patients with breast cancer, approximately 75% have elevated expression of estrogen receptor (ER). Knowing the hormone receptor status of cancer is important in designing effective treatment and predicting disease prognosis. In addition to breast cancer, there are other estrogen-dependent diseases such as uterine and ovarian cancer that need appropriate diagnosis methods. Current common diagnostic methods, including MRI, PET, and CT scan, fail to provide an in-time data about disease prognosis due to lack of an appropriate molecular probe.
A molecular probe with high affinity and selectivity to estrogen receptor would yield data not provided by other molecular agent and imaging modality as it would directly indicate the receptor status of the suspected lesion. The available estrogen-derivative molecular probes in clinical use are produced through low-yield synthesis procedure and need careful chromatographic separation to be purified. Even after clinical use, they are rapidly metabolized, which results in suboptimal tissue concentration and selectivity. Additionally, the generated metabolites accumulate and produce high background signals that compromise the detection of lesion. Hence, new molecular probes with higher selectivity and stability should be designed to enhance the early diagnosis of ER-positive diseases.
Technology Overview
Researchers at Northeastern invented a novel family of molecular imaging agents that target the estrogen receptor and can be used to visualize tissue containing those receptors with a variety of imaging modalities. The molecular probe uses high-affinity 11-beta substituted steroidal antiestrogen to provide ER selectivity and affinity. This estrogen derivative is synthesized by a modular method, which increases the synthesis yield to more than 80% and enables incorporating different linkers that enhance the affinity of the agent. This molecular probe has reduced liver metabolization and has higher renal clearance due to its hydrophilic nature. The 11-beta substituent is modified with a chemically reactive terminal group to which a variety of imaging groups can be appended without affecting core ER-selectivity or binding properties. Some of these imaging groups include fluorine, gallium, radio-iodine, technetium, and near IR dyes. Thus, 11-beta substituents coupled with these imaging groups is suitable for use in different imaging modalities including PET, SPECT, fluorescence, MRI, and Raman. Such modalities allow the probe to be used for imaging the cell, tissue, or the whole body, which makes the probe useful for diagnosis and other purposes such as drug discovery.
Benefits
- Modular synthesis strategy
- Higher synthesis yield
- Higher affinity for estrogen receptor
- Lower liver uptake and greater renal clearance
- The possibility of using in various modalities
Applications
- Diagnosis of estrogen-dependent diseases such as breast, uterine and ovarian cancer
- Measuring receptor occupancy in drug discovery
Opportunity
- License
- Partnering
- Research Collaboration
