For more than 20 years, University of Colorado School of Medicine experts led by E. David Crawford, MD, have been applying new technologies to help diagnose and treat prostate cancer. Back in the 1990s, they pioneered the computer modeling of the prostate gland itself. In the 2000s, they were the first to do 3D mapping biopsies and targeted focal treatment using lasers at University of Colorado Hospital (UCH). Now they’re behind a system that uses a different kind of light in hopes of bringing relief to the million or so men who undergo prostate biopsies each year.
The goal is to send men home from biopsy appointments with a good idea of whether or not they have prostate cancer and how pervasive it might be – rather than waiting days for biopsy results. And because the approach requires, on average, far fewer biopsy samples (called “cores”), patients should suffer less discomfort with lower risk of infection and bleeding as a result of the procedure.
The new technology, called the ClariCore Biopsy System, is under development at Precision Biopsy, which in June became the first tenant in CU’s new Biosciences 2 building. But ClariCore is on the march to market, says Crawford, head of Urologic Oncology at CU. Crawford hatched the idea and has tested a prototype system at UCH with striking results. The company recently landed $33.6 million in funding, in part to speed ClariCore’s path to commercialization.
Seeing the light
ClariCore, which licenses its core technology from CU, has been more than a decade in the making. Crawford first approached longtime collaborator Priya Werahera, PhD, an associate professor in CU’s departments of Pathology and Bioengineering, about the idea in 2002. Ninety percent of prostate biopsy cores turn out to be normal and free of cancer, he reminded Werahera. “Crawford wanted to know right away: Is this a tumor or not?” Werahera recalls.
Werahera brought in John Daily, PhD, a CU Boulder professor of mechanical engineering, and CU School of Medicine pathologist Scott Lucia, MD, who directs CU’s Prostate Diagnostic Laboratory. They looked into using a tumor-detecting technology better known for its use in explosives testing and sorting out the composition of celestial bodies: optical spectroscopy. Spectroscopy determines what something is made of based on how it interacts with light. In this case, they focused on fluorescence spectroscopy, which involves shining particular wavelengths of light at tissues and then capturing the light that emits back off them.
Researchers have long known that cancerous tissues have different chemical signatures than healthy cells. Cancers eat into the collagen matrix so there’s less of it. They also produce more NADH, a coenzyme central to cellular energy production and have lower levels of the amino acid tryptophan than healthy cells.
Fluorescence spectroscopy can shed light on all this. The challenge, Werahera says, was in the packaging. To work real-time during a routine prostate biopsy, he and colleagues needed to figure out a way to emit and receive the light through a biopsy needle while not interfering with the needle’s ability to snip tissue cores. The system would also demand hardware and software in the procedure room to process the results and display them for the physician.
They brought in the University of Colorado Anschutz Technology Transfer Office (TTO) in 2005, which assisted with intellectual property as well as business and product planning. The TTO also supported a group of CU Boulder undergraduate mechanical engineering students as they worked on possible biopsy needle designs to capture optical spectra of tissue. National Institutes of Health and State of Colorado Bioscience Discovery Evaluation grants helped move development ahead.
By 2008, Werahera, Daily, Lucia and Boston, Mass.-based Allied Minds had co-founded Precision Biopsy; Werahera still serves as chief scientific officer. Edward Jasion, one of those CU engineering undergrads, is now Precision Biopsy’s senior project engineer.
In 2012, Crawford put a system developed by Precision Biopsy to the test at UCH. Thirteen men who were having their prostates removed agreed to let Crawford and colleagues test the ClariCore forerunner, both before the gland was removed and also afterward. Crawford advanced the biopsy needle into the exposed prostate with the blood supply to the gland still intact. Diodes in a console emitted light at two wavelengths (290 and 340 nanometers) through several optical fibers and channeled the reflected light back through a separate, dedicated optical fiber. When the needle was in the prostate, Crawford took fluorescent spectra and biopsy cores for spectral correlation and microscopic analysis of diseased tissue.
The results were striking. Tissue analysis confirmed that the system correctly identified 84 percent of the actual cancers in vivo (i.e., prostate still in the patient) and was correct 94 percent of the time in identifying a cancer-free spectroscopic sample. Crawford called the results “unbelievable.”
“Nothing’s 100 percent, not
even a biopsy,” he acknowledged, but “anything that high is good.”
For patients, in addition to having a good idea of their status in real-time, there will be fewer biopsy cores removed as the physicians need only snip when there’s a suspicion of disease (though they can choose to take as many samples as they feel necessary). Crawford says that could mean one or two cores removed rather than the typical 10 to 12 while also eliminating the need for repeat biopsies.
Work to do
In the newest version of ClariCore, a single fiber-optic line will serve to both send and receive light and the biopsy handpiece will automatically advance the needle 1 millimeter at a time. There is a console designed to fit nicely into the urology procedure environment. The company is also adding a second type of spectroscopy, called elastic-scattering, which is designed to recognize the tissue deformities inherent in tumors. The combination of fluorescence and scattering spectra could further boost the system’s diagnostic accuracy, Werahera says.
They’ll know if that’s true soon enough. Crawford is now preparing to try out the new system on consenting patients. If all goes well with that clinical trial and follow-ons at other institutions, results will be submitted to the U.S. Food and Drug Administration for approval. The recent cash infusion will, in part, go into these trials, commercial expansion, and development of a focal therapy program that combines the ClariCore’s diagnostic prowess with a means of doing real-time targeted treatment for patients, all in one session, Precision Biopsy officials say.
Farther down the road, the same technology has potential to be applied to other tumors – kidney, liver, lung, breast – about anything that requires a biopsy, Crawford says.
“To see this come to fruition is just great for patients, and it’s something I think that we at the University of Colorado and the UCHealth system can be really proud of,” Crawford said.