CLEVELAND, Ohio – Women who have undergone a lumpectomy to remove a cancerous tumor from their breast – and the surgeons who treat them – don’t know for several days if the tumor has been completely removed.
A professor at Case Western Reserve University and his two partners hope that their patented guided imaging technology will one day eliminate the need for repeat lumpectomies (something that between 20 and 60 percent of women must endure) and also will save money in the process.
The technology – which also has potential applications with skin cancer surgery — could be available in hospitals within three years, if Akrotome Imaging Inc. is able to secure the funding needed to build a prototype of the machine behind their technology and conduct a larger clinical trial.
The imaging technology is a fluorescent molecular probe that is applied to a tumor after surgical removal to help surgeons determine if they have removed all of the cancerous tissue.
The probe is not an instrument in the traditional sense, but rather a molecular entity that is sprayed onto the tissue and works as a contrast agent.
If the area lights up, it’s an indication that cancer is still present. Before closing the incision, the surgeon can remove more of the surrounding normal tissue to ensure that the entire tumor has been removed.
Unlike other imaging technologies like a PET scan, this one doesn’t require the use of any chemicals injected into patients.
Basilion, a professor in the departments of radiology, biomedical engineering and pathology at CWRU and co-director of the Cancer Imaging Program for the Case Comprehensive Cancer Center, uses the image of a hard-boiled egg to explain the need for their technology.
Not only is the cancerous lump removed during a lumpectomy, in which the breast is spared, but normal breast tissue is also removed.
“The yolk is the cancer and the white is the normal tissue,” Basilion explained. “You want to take out enough of the white so there is no yellow … the tumor is contained completely within normal tissue and you’ve gotten it all.”
But oftentimes that is easier said than done, when surgeons are trying their best to estimate visually where the cancer stops and where healthy tissue begins.
“If you talk to a surgeon… when a patient says to them, ‘Did you get it all?’ They hate saying, ‘I don’t know. We have to wait for pathology,’ ” said Straight, of West Lafayette, Indiana, who joined Akrotome as president and CEO in 2012.
“Most of them will tell you, that is a completely unacceptable answer for them to have to give, and they want to give a better answer and say, ‘Yes, I’m pretty sure we got it all.’ And this technology allows them to do that.”
A collaboration that spans thousands of miles
Molecular imaging emerged in the 1990s as a way to provide physicians with detailed images of what is happening inside of the body. But creating optical imaging technology that could be used outside of the body, as opposed to the positron emission tomography (PET) scan, proved to be more difficult, given that tissue, water and blood absorb light.
Nearly a decade ago, Basilion started working on a non-invasive way to identify the presence of cancer. But he didn’t want to focus on something that had to be injected or ingested for a tumor to glow, because then the item would have to go through the lengthy – and costly – Food and Drug Administration regulation process.
Instead, Basilion decided to create something that could capitalize on the demonstrated ability of proteases, the enzymes that help cancer spread through body tissue, to turn on imaging probes.
He had an idea of developing something that could be sprayed in the tumor cavity, and creating imaging cameras that could be placed near the area. Within a matter of minutes, areas where traces of cancer remained would light up.
Enter Bogyo, a professor of pathology, microbiology and immunology at Stanford University School of Medicine.
The two men met at an imaging meeting in Germany and started talking, trading stories about their latest projects.
Bogyo told Basilion that he was developing molecules for highlighting protease enzymes. His goal was to create a substance that could light up any evidence of cancer tissue.
Basilion asked Bogyo if he could license Bogyo’s technology in order to further develop his idea for the imaging probes.
Not only did Bogyo say yes, but he sent Basilion the reagents. The two began collaborating, eventually forming Akrotome, which was incorporated in May 2008.
Mouse studies conducted at CWRU using an agent sprayed after surgery to remove brain tumors worked well to highlight residual cancer.
“We could see things [the surgeons] couldn’t see with the visible light,” Basilion said.
But developing a spray to be used in humans during surgery would still have to go through lengthy FDA regulations. So they tweaked their method again.
Basilon has received approval to conduct a clinical trial involving human tissue samples to validate the technology for breast cancer.
Before the tumor samples are sent to pathology, they are sprayed with the reagent. Five minutes later the samples go into an imaging device. If bright spots appear, it means that the tissue is 2 mm or less from the cancer/non-cancer border – an incomplete surgery.
To date, tumor samples from 25 patients have been sprayed, with an accuracy rate of around 75 percent in detecting cancer. Samples from 30 more patients are needed for the results to be statistically significant.
In the past the company has received some federal grant money, targeted to small businesses conducting research, and some state funding.
Akrotome is now applying for other funding, and hope to pique the interest of local investors who can help move their work forward.
The next step is to build a device that can capture images of the tumor from all sides, and is small enough to be portable so it can be moved easily in and out of an operating room.
“There’s a good investment ecosystem in this area,” Straight, whose work history includes co-founding two bio companies, said of northeast Ohio.
“But when you look at clinical technologies, people see risk as soon as they look at them,” he said. “We’ve spent a lot of time de-risking the investment as much as possible [through lots of clinical-grade research to demonstrate the technology’s effectiveness].”
It won’t be the most exciting technology in the world, Basilion concedes. “But it works, and it’s simple,” he said.
“It’s that impact that we think we have a leg up on the competition.”