Aggressive metastatic breast cancer is tough to treat and patients rarely survive two years beyond diagnosis. Researchers at Johns Hopkins University (Baltimore) have fabricated nanoparticles that can work liked guided missiles to carry radioisotopes through the body and deliver them selectively to tumors specifically for this type of deadly cancer.
"Instead of delivering radioactive therapy from outside the body, we're administering it from inside," George Sgouros, PhD, director of Radiopharmaceutical Dosimetry Section, Division of Nuclear Medicine, Johns Hopkins University, School of Medicine, told Medical Device Daily. "In a sense, it's a guided missile because it recognizes a tumor and, when it gets there, radiation is delivered from within, avoiding irradiating normal tissue and side effects."
Sgouros will report the latest results of his research, including studies in animal models, today at the 51st meeting of the American Association of Physicists in Medicine (College Park, Maryland) in Anaheim, California.
Sgouros and his research team are using liposomes – fat bubbles – that have been modified with antibodies, a class of immune system proteins that recognize and bind to many different microscopic targets such as bacteria, viruses, other proteins and human cells. Some antibodies specifically bind to cancer cells, and by attaching these cancer-specific antibodies to the liposomes, the scientists have created immunoliposomes. They move through the bloodstream and seek out tumors. When they come into contact with their target cells, they deliver their payload.
"My lab is focusing on alpha particle emitters," Sgouros said. "It's a much shorter range, but more potent type of radiation. It's also harder to deliver and may be more toxic. We're at the preclinical phase, studying how to optimize delivery and reduce normal organ toxicity in the setting of metastatic disease."
In Sgouros' presentation today, he'll discuss how liposomes are the prototypical nanodevices for delivery of therapeutics. The little structures that average 100 nm, also known as nanovesicles, comprise a phospholipid membrane, an encapsulated aqueous phase containing the therapeutic agent and surface grafted polymer chains.
Because tumor vasculature is leakier than normal organ vasculature, the nanoparticles are better able to find them.
"We are using antibodies that recognize tumor cell surface antigens," Sgouros said. "This makes them stay at the tumor site longer once they reach the tumor cells."
Once they reach their targets, the half life of the radio radionuclides is 45 minutes. About five hours later, there is very little irradiating tissue remaining and the nanoparticles clear the body via urine and feces. By a week later, they are completely cleared from the body.
Targeted radionuclide therapy is not new. GlaxoSmithKline's (London) Bexxar is an FDA-approved radioimmunotherapeutic drug for non-Hodgkin's lymphoma (NHL). Spectrum Pharmaceuticals' (Irvine, California) Zevalin – also FDA approved – is for patients with relapsed or refractory, low-grade or follicular B-cell NHL, including patients who are rituximab-refractory or rituximab-na ve. Spectrum is now seeking approval of Zevalin as first-line consolidation therapy for NHL.
But Sgouros and team are aiming their version of the nanoparticles at metastatic breast cancer. So far, it seems to be working in mice.
"It's an approach that's quite optimal for disseminated disease," he said. "You can think of it as being analogous to chemotherapy with much fewer side effects. It's an early start, but it's encouraging. We've shown that we can make these things and that they are stable over time. "
His team has managed to package more powerful radioisotopes, called alpha-particle emitters, specifically designed to attack aggressive-type metastatic breast cancer. The early results prove the larger dose of radionuclides can be packed into the liposomes and substantially extend the life of treated mice.
Sgouros wouldn't venture to predict when it would be ready to test in humans. He's been working in targeted radioactive nanoparticles for the past five years.
His team's work is funded by grants from the National Cancer Institute and the Department of Defense.
"We're really focused on getting these in humans," he said. "The emphasis now is on more engineering. The stability is already good. But we're trying to increase the amount of radionuclide to deliver. When we get that working, we'll spend time on formulations for FDA review. Then we'll need an industry partner."