Stony Brook University’s Boros Lab has begun a new stage in its research of radioactive scandium isotopes in medical chemistry, with the goal of creating a new treatment for prostate cancer.
The principal investigator of the Boros Lab and an assistant professor of chemistry, Eszter Boros, Ph.D., said that more ambitiously, the research could lead to a new production method for creating purer radiotherapy drugs and diagnostic tools for many different cancers. To fund her research, Boros will be using a $825,000 grant from her win as a 2020 Moore Inventor Fellow, as well as a $643,950 grant from the National Science Foundation’s 2020 CAREER Award.
“What we’re trying to do as part of the Moore Fellowship is take it a step further,” Boros said. “What we want to try to do is now make not just one kind of imaging agent [supercategory that contains radiotracers], but many different kinds of imaging agents, and do that in a specific way.”
The Moore Inventor Fellowship is funding the further development of a method to create an entirely new radiotracer molecule that can be used in detecting prostate cancer with a positron emission tomography (PET) scanner, as well as the adaptation of this method for other radiotracers.
A radiotracer is a compound containing a radioactive metal ion, a targeting molecule that attaches to certain cell receptors and a molecule that connects the two if they cannot connect naturally. In Boros Lab’s research, the metal ion is scandium-44.
A radiologist who suspects something is wrong with a patient’s internal chemistry, such as a cancerous tumor, would either inject the radiotracer into the patient or have them swallow or inhale it, and then put them into a PET scanner after the radiotracer has had time to circulate. The radiotracer searches for a specific molecule that is unique to the surface of the type of cancer cell that it is looking for — almost like a puzzle piece looking for its match. The scanner would show where the radiotracer has attached in the body and the radiologist would then diagnose the patient based upon the scanner image and which type of radiotracer was used.
Scandium-44 has seen little use in medicine before.
However, the Boros Lab study that piqued the Moore Foundation’s interest when they applied for the fellowship spurred the latter to create a new molecule known as a bifunctional chelator — a molecular structure that can attach to both a metal ion and a targeting molecule. The bifunctional chelator is being used to prove that it can be utilized as part of a functioning scandium-44-based radiotracer.
“The real innovation is that we found something that works at room temperature and works pretty quickly,” Brett Vaughn, a chemistry Ph.D. student at the Boros Lab, said. Scandium-based radiotracers that had been devised before had required high-temperature environments to be created.
The members of the lab chose prostate cancer as a test case because the efficacy of the targeting molecules for detecting and attaching to prostate cancer cells without false positives has been thoroughly proven. Thus, if the results did not turn out well, the team could rule out a problem with the targeting molecule.
There are also some issues that could be worked out with current radiotracers for prostate cancer.
“Materials that are currently used for imaging tumors are also taken up in the liver and other parts of the body,” Grace Ahn, Ph.D., the Boros Labs’ post-doctoral fellow, said.
The method currently used could possibly lead to smaller tumors being missed, or tumor size and spread underestimated with the current radiotracers. However, the results in mice from Boros Labs’ new Scandium-44 radiotracer have been clear as day.
“Once the image of our tracer was done processing … we took a minute off and the three of us just crowded around the computer monitor to gaze at the really beautiful image,” Ahn said. “We saw a bright red tumor and bladder … the activity was just in the tumor and the bladder.”
The Boros Lab is one of only a few labs on the Stony Brook University West Campus that are allowed to work with radioactive materials, which presents unique issues — both with safety regulations and with the lab work itself.
At the moment, neither Stony Brook University nor Stony Brook Medicine has the ability to produce radioactive material. Once the pandemic is over, Stony Brook Medicine does plan to continue their installation of a cyclotron, a particle accelerator used for creating medical isotopes. But for now, all radioactive material used in campus labs has to be produced elsewhere and shipped to Stony Brook University for use.
The scandium-44 samples used in Boros Labs’ studies come all the way from the lab of John Engel at the University of Wisconsin-Madison. This requires express shipping, as a half-life of scandium-44, or the time it takes for half of a sample to decay into a nonradioactive element, is only four hours.
“They made it on a Tuesday … mailed it to us overnight,” Vaughn said. “After 24 hours … there’s a lot less of it left … we had to work very quickly.”
Vaugh said that the short half-life is perfect for medicinal purposes, according to the “As Low As Reasonably Achievable” principle for working with radioactivity. It matches well with the time it takes for the maximum amount of their radiotracer to accumulate in the prostate.
“A half-life that’s matched well to the application is a really favorable characteristic,” Vaughn said.
Even with the relatively safest radioactive isotopes, precautions are still taken. Materials are stored in locked boxes or locked refrigerators depending on the chemistry involved.
“If it’s not locked and secured, the lab door has to be locked and secured,” Colleen Shea, the associate radiation officer for medical school research and the cyclotron, said.
More energetic isotopes, which give off larger quantities of harmful radiation, have to have their boxes and refrigerators lined with lead or other shielding materials.
While Boros Labs’ work is still far from human trials, the implications of Eszter Boros’s work and the work of her lab are exciting for the future of cancer treatment.
“There is great potential that therapy can be improved… for prostate cancer,” Dr. Dinko Franceschi, the chief of nuclear medicine at Stony Brook Hospital, said. “But potentially, it can be used for other kinds of cancers if you have a suitable targeting molecule.”