Executive Summary
Radiology researchers at the University of Virginia and Cedars-Sinai Medical Center have developed novel heptamethine dyes that possess both nuclear and near-infrared imaging capabilities for imaging, targeting and detecting tumors. While this imaging technique is being specifically developed for invasive breast cancer, there are future possibilities of applying it to prostate and other cancers.
Background
Breast cancer remains one of the most prevalent cancer diseases in women of developed countries The American Cancer Society (ACS) estimates that 226,870 new cases of invasive breast cancer and 39,510 breast cancer deaths will occur among women in the U.S. during 2012, making breast cancer the second most diagnosed and the second most deadly cancer among women.
Mammography can often detect breast cancer at an early stage but identifies only about 80–90 percent of breast cancers in asymptomatic women and carries a high rate of false positives. The ACS currently recommends annual screening using magnetic resonance imaging (MRI). Like mammography, however, MRI carries high false positive rates. Additionally, only 16 percent of additional disease is diagnosed with MRI.
Heptamethine dyes are a promising class of compounds that can be used for improved in vivo cancer imaging. They have intrinsic fluorescent properties at near-infrared (NIR) wavelengths, negating the need for chemical conjugation of a fluorophore. Previously discovered heptamethine dyes have been shown to detect tumor xenografts and spontaneous metastases in mice with a high degree of sensitivity. Additionally, these molecules are preferentially absorbed and retained in cancer cells but not normal cells, show no systemic toxicity and are rapidly cleared. However, drawbacks of current NIR imaging include severe attenuation of NIR light at depths greater than 1 centimeter and limited scope of specific cancer applications.
About the Invention
U.Va. researchers, in collaboration with researchers at Cedars-Sinai, have discovered novel compounds that possess both the intrinsic near-infrared (NIR) properties typical of heptamethine dyes and nuclear imaging capability. These small molecule radio-/NIR hybrid tracers are derived from the heptamethine dye MHI-148, which exhibits high specificity to a broad spectrum of cancers.
In a mouse model of breast cancer, researchers successfully visualized real-time uptake of the compounds in the xenograft breast tumor. By administering the dual imaging tracer to a breast cancer patient followed by performing a PET or SPECT scan, tumors and metastases can be effectively identified, imaged and localized.
The current invention is not limited to breast cancer; the researchers have also provided a mouse model of metastatic prostate cancer. ARCaPm prostate cancer cells were injected into a mouse and the mouse was examined by NIRF imaging with the compounds, which reveals the metastatic tumors formed in the mouse.
Ongoing studies include validating imaging capabilities of small metastases for intraoperative surgical guidance in a mouse model of metastatic breast cancer. The use of this dual imaging agent during surgery will benefit cancer patients by lowering the number of surgeries, decreasing costs and improving surgical outcomes. U.Va. researchers are also synthesizing new derivative compounds, conjugating to therapeutic agents and assessing efficacy in mouse models.
For more information, see http://www.ncbi.nlm.nih.gov/pubmed/23375364.
Advantages
This invention offers the following advantages over current alternatives:
- Provides dual imaging capabilities
- May be applied to many other cancer types
