Boston Scientific’s microscopic TheraSphere devices go from nuclear reactors to tumors to kill cancer

Boston Scientific’s cancer-killing TheraSpheres are smaller than a human hair and forged in 1,500°C temperatures. […]

Boston Scientific’s cancer-killing TheraSpheres are smaller than a human hair and forged in 1,500°C temperatures.

But it’s the time spent inside a nuclear reactor that gives these microscopic catheter-delivered devices the radioactive power to stop liver cancer tumors from growing — or even shrinking them.

Boston Scientific Interventional Oncology President Peter Pattison has advanced TheraSphere throughout his career, first with Nordion and then BTG.

Nordion licensed the technology from the University of Missouri in 2001 and developed TheraSphere before selling it to BTG, which Boston Scientific acquired for $4 billion in 2019.

“I came in pretty green as an MBA student,” Pattison said in an interview with Medical Design & Outsourcing. “… We turned it into a one-year project at at Nordion: What do we do with this technology? Do we license it to another company? Do we have the chops to launch a medical device?”

Today, TheraSphere is now part of Boston Scientific’s interventional oncology portfolio, winning FDA premarket approval (PMA) in 2021 as selective internal radiation therapy (SIRT) for certain liver tumors.

Boston Scientific — the world’s 12th-largest medical device company —  is now exploring other applications for the technology, including a first-in-human trial for brain cancer.

How TheraSphere works

“What radiation oncology tries to do every day — with every new software release, every new machine — is try to get more and more dose to the tumor with less and less dose to the healthy tissue,” Pattison said. “… The concept of TheraSphere is if I make these beads small enough, I can get an ultra high dose of radiation into the tumor with a minimal amount of those beads sitting around in the healthy tissue?”

Interventional radiologists apply the radioactive TheraSphere beads to a patient’s liver tumor using a standard microcatheter, injecting the beads and saline just outside the tumor in the bloodstream supplying it.

Each of these biocompatible beads measure somewhere between 15 to 35 microns in diameter, making them small enough to flow with the blood into a tumor. For comparison, red blood cells are about 6 microns in diameter.

“We want to create these beads where we can be sure to get them into the tumor delivering a high payload of radiation, but not so small that they’re going to trundle out the other side [and] free-flow throughout the body systemically,” Pattison said. “… We found the right type of bead with the right type of material — glass — with the right type of isotopes. This was a custom-designed treatment to really take advantage of liver vasculature and liver tumors.”

Those isotopes are yttrium-90, which emits pure beta radiation about 2 to 2.5 mm from the beads.

“As soon as you’re treated, you can go and hug your loved ones and sleep in the same bed as your spouse,” Pattison said.

The yttrium-90 has a half-life of about 2.7 days, meaning the radioactivity wanes over about four weeks. After that the glass spheres are inert, but remain inside the patient.

When placing TheraSpheres inside a patient, the interventional radiologist uses contrast to visualize the blood vessels feeding into the tumor to determine where to place the catheter to deliver the radioactive beads.

“Sometimes there will be vessels feeding one side of the tumor and vessels feeding another side, so they may deliver a dose on one side and then get another dose and deliver it from the other side. It really depends on that on that physician how close they want to get,” Pattison said.

He also described a technique called radiation segmentectomy to eliminate cancer cells that may have spread beyond the tumor itself.

“The name of the game of destroying a tumor is getting margin around the tumor. Once the tumor gets to 3 cm or more there’s probably little bits of cells of cancer outside the main tumor that you can’t see with the naked eye. Tumors more than 2 cm often can come back for that reason — you’ve got the tumor, but there’s probably microsatellites of cancer cells now outside of that tumor,” he said. “Radiation segmentectomy is a really fascinating technique where if the patient has enough healthy liver reserve, they can pull that catheter back enough to get a whole segment — the liver’s divided into eight segments — and completely destroy an entire segment of the liver. If the patient has enough liver reserve, that’s a great outcome because you’ve got the tumor, and you’ve got a lot of that margin around the tumor.”

“In our studies, principally our legacy study that led to our FDA PMA in 2021,” he continued, t”hat’s what we were able to show. [By delivering] an ablative dose that really goes out for a segment, you can get very long-term survivals.”

How TheraSpheres are manufactured

The TheraSphere microspheres are made with aluminum oxide and silicon oxide (two common ingredients in high purity, medical-grade glass), plus stable, inactive yttrium-89. This mixture is melted into glass at 1,500°C and cooled to form microscopic spheres of various sizes, with microspheres small enough for TheraSphere sifted out.

Then, those microspheres are placed in an ampule and hit with high-speed, high-energy neutrons inside one of the research reactors Boston Scientific partners with to transform the yttrium-89 into yttrium-90.

A patient’s individual dose is millions of TheraSphere beads, but because they’re so small it only might weigh a few dozen milligrams. Boston Scientific’s nuclear partners create several grams of radioactive Theraspheres at a time in ampules sent into the reactors.

Embedding yttrium inside the glass matrix allows for what Boston Scientific calls an “unmatched radioactive concentration” versus other approaches, like using resin to bind a coating of yttrium-90.

“You just can’t get as much in there per bead like you can with TheraSphere,” Pattison said.

He credited TheraSphere’s success to the combined expertise of the technology’s co-inventors from the University of Missouri system: ceramic engineering researcher Delbert Day and MURR nuclear scientist Gary Ehrhardt.

“They identified the problem and they purpose-built this product with the best material and the best radiation [to] come up with the best product,” Pattison said.

Future applications

Boston Scientific is looking into using TheraSphere to treat prostate cancer, lung cancer, kidney cancer and other kinds of cancers with tumors that are radiosensitive and can be visualized and accessed with a catheter.

“The loose scientific theory is if tumors are hypervascular — most of them are — and you can see it and you can get a catheter there, you should be able to deliver a super high dose of radiation at the tip of this catheter,” Pattison said.

But for now, Boston Scientific’s Frontier trial is studying the safety and feasibility of using TheraSphere to treat recurrent glioblastoma in the brain.

“It’s recruiting and we think it’s going well,” Pattison said. “We’re trying to prove that TheraSphere is the best way to deliver a high dose of radiation to very small space.”

Look for more from this interview with Boston Scientific’s Peter Pattison at Medical Design & Outsourcing in the coming weeks, including supply chain challenges, a unique partner, and lessons for other device developers.

Original Article: (https://www.medicaldesignandoutsourcing.com/boston-scientific-therasphere-radiation-oncology-cancer-treatment/)