In a breakthrough for medical imaging, scientists at the University of North Carolina's Lineberger Comprehensive Cancer Center have discovered a method for creating radioactive tracers to better track pharmaceutical products in the body, as well as image disorders such as cancer and other medical conditions.
The researchers reported in the journal Science a method for creating tracers used with positron emission tomography, or PET, imaging. Researchers said their findings may allow for the attachment of radioactive tags to compounds that were previously difficult or even impossible to label.
"Positron emission tomography is a powerful, fast-developing technology that plays key roles in medical imaging and drug discovery and development," said study author Zibo Li, PhD, an associate professor at the UNC School. of the Department of Radiology Medicine, and director of the Cyclotronics and Radiochemistry Program at the Biomedical Research Image Center of UNC. "This discovery opens a new window for generating new PET agents from existing drugs."
PET scans trace a radioactive tag attached to a compound. These tracers are usually injected into the body and produce bright images on medical examinations as the tracer accumulates in the target lesion, organ or tissue. Scientists can attach tags to molecules such as glucose that will accumulate in tumors as cancer cells consume sugar to boost their hyperactive growth, or to amino acids that, like building blocks of proteins, can be highly consumed in tumors . They can also attach them to potential new medications to keep up with their course in the body.
"Tumor molecules are believed to absorb these features faster than healthy cells," said David Nicewicz, PhD, a professor in the chemistry department at UNC-Chapel Hill and co-author of the study. "What we have contributed to the field is a new method for introducing radiolabeled isotopes of atoms into drug molecules in a way that has not been done before."
In their study, the researchers described a new way of connecting the radioactive molecule Fluorine-18, an isotope widely used in PET imaging, breaking down a specific chemical structure of carbon and hydrogen atoms. In the presence of blue light from a laser and after the addition of a catalyst material to accelerate the reaction, researchers could break the chemical bonds in the structure and insert Fluor-18. Once connected, the plotter emits gamma rays that are captured by the image. The researchers used a cyclotron, a particle accelerator, at the UNC Biomedical Research Image Center to create Fluor-18.
Researchers predict multiple potential applications for their discovery, including medical imaging to track patients in response to a drug, or to aid in drug development research.
"Not only can we study where drugs are located in the body, which is important for the development of medications, but we can also develop imaging agents to monitor the progression of cancer or inflammation in the body, aiding in cancer research and Alzheimer's ". Nicewicz said. "Having more than one method for detecting tumors can provide cross-checking to make sure what you're seeing is real. If you have two methods for validating a scan, two are better than one."
Although existing radiolabeling methods require the synthesis of new compounds dedicated to attaching radiotag, researchers say their approach may allow them to put a mark on existing compounds – a benefit for drug development research.
"In this study, we showed that we could label a broad spectrum of compounds," Li said, including anti-inflammatory drugs, and specific amino acids to show that they could see tumors.
Li also said that the information obtained by the new PET can help in the development of corresponding treatment plans depending on the outcome of the image, which would be an important step in the supply of personalized medicines.
The researchers said the next step is to develop a device that makes it easier for scientists to use this new method to create radiolabeled tracers. In addition, they are working to expand their technology to develop other trackers that use a different radioactive material, such as Carbon-11.
"This discovery opens a new window for generating new PET agents from existing drugs," Li said. "Many too complicated, or almost impossible to label, could potentially work using this method."
In addition to Li and Nicewicz, other authors include Wei Chen, Nicolas E. S. Tay, Benjamin Giglio, Wang Mengzhe, Wang Hui and Wu Zhanhong.
The study was supported by the National Institutes of Health, the UNC Department of Radiology, the Center for Images of Biomedical Research and UNC Lineberger. Tay is supported by a postgraduate research grant from the National Science Foundation.
Conflict of interest: Tay and Nicewicz and inventors in a technology-related patent filed by UNC, and currently pending.