Researchers at the Paul Scherrer Institute (PSI) in collaboration with Inselspital-Bern University Hospital have developed a promising new radioimmunotherapy for lymphoma using the radioactive isotope terbium-161. The findings, published in the Journal of Nuclear Medicine, demonstrate significant therapeutic advantages over current radionuclide treatments and could offer new hope for patients with this challenging cancer.
Targeting Lymphoma with Precision Radiation
The innovative therapy involves attaching terbium-161 to an antibody that specifically targets the CD30 receptor, a structure particularly abundant in lymphoma cells. "The radioactive isotope terbium-161 is attached to an antibody and injected into the bloodstream of the patient," explains Martin Béhé from PSI's Center for Radiopharmaceutical Sciences. "This brings the radioactive terbium directly to the site of the tumor to kill the cancer cells with its radioactive radiation."
This targeted approach could benefit nearly one-third of all lymphoma patients whose tumor cells produce the CD30 receptor. The therapy also shows promise for T-cell lymphomas, where immune system T-lymphocytes become cancerous—a disease that has historically been difficult to treat.
Superior Performance Over Current Standards
Terbium-161 offers distinct advantages over lutetium-177, the radioactive substance currently used in clinical radionuclide therapy for prostate cancer and hormone-producing tumors. While lutetium-177 emits high-energy beta particles effective against larger tumors, individual tumor cells and small cancer clusters can evade treatment, leading to disease recurrence.
The key advantage of terbium-161 lies in its emission profile. In addition to beta particles, it emits conversion and Auger electrons with a range of less than one micrometer—approximately the size of a tumor cell. "This radiation has a range of less than one micrometre, or one thousandth of a millimetre. This is the size of a tumor cell," Béhé notes.
"Terbium-161 fires more precise bullets, so to speak," explains Elisa Rioja-Blanco, first author of the study. This precision allows the therapy to eliminate individual cancer cells circulating in the bloodstream without causing severe side effects to healthy tissue.
Remarkable Preclinical Results
Laboratory testing revealed the superior efficacy of the terbium-161 therapy. When tested on three types of cancer cells producing CD30 receptors, the terbium-based treatment was 2 to 43 times more effective at killing cancer cells compared to the analogous lutetium-177 substance, depending on cell type.
Further investigation revealed that the enhanced effectiveness stems from the terbium-based drug causing more severe DNA damage in cancer cells—damage that the cells cannot repair themselves.
The therapy's promise was further validated in mouse studies. "This shows us where the substance accumulates in the body and whether it actually reaches tumors," Rioja-Blanco explains. The results were striking: mice treated with terbium-161 survived twice as long as those receiving lutetium-177 treatment, with some animals achieving complete cancer remission.
Clinical Translation on the Horizon
The isotope's 6.9-day half-life provides practical advantages for clinical implementation. This timeframe allows for drug transportation to hospitals without significant activity loss while ensuring radiation levels decrease rapidly after treatment.
While terbium-161 is already being tested as an anti-cancer drug in several clinical trials, the PSI researchers represent the first team to investigate its potential specifically for lymphoma treatment. "Our results are a good indication that the substance could also prove to be effective against lymphoma in humans," says Rioja-Blanco.
The research team has secured follow-on funding from Innosuisse to further investigate and optimize the drug for commercialization and future human testing. The Lymphoma Challenge, organized by ETH Zurich, provided financial support for the initial project.
With nearly 2,000 people diagnosed with lymphoma annually in Switzerland alone, and approximately 570 deaths from the disease each year, this targeted radioimmunotherapy approach could significantly impact patient outcomes in a field where treatment options remain limited.
