A groundbreaking study from the Paul Scherrer Institute (PSI) in collaboration with Inselspital–Bern University Hospital has unveiled a promising new therapy for lymphoma using the radioactive isotope terbium-161
This innovative breakthrough, detailed in the Journal of Nuclear Medicine, involves attaching terbium-161 to an antibody that targets the CD30 receptor, which is present in many lymphoma cells.
Researchers at PSI’s Center for Radiopharmaceutical Sciences are now proposing a new therapy that could soon increase the chances of survival for many individuals affected: radioimmunotherapy using the nuclide terbium-161.
“The radioactive isotope terbium-161 is attached to an antibody and injected into the bloodstream of the patient,” explained Martin Béhé from the Center for Radiopharmaceutical Sciences, part of the PSI Center for Life Sciences. This antibody latches onto a structure in the body that is particularly common in lymphoma cells: the CD30 receptor. “This brings the radioactive terbium directly to the site of the tumour to kill the cancer cells with its radioactive radiation.”
Radionuclide therapy has proven effective in treating several other types of cancer
Radionuclide therapy is already a well-established approach in clinical practice. Hospitals currently use a different radioactive substance—lutetium-177—for treating prostate cancer and tumours originating from hormone-producing cells. As it decays, lutetium-177 emits high-energy beta particles, which are particularly effective at targeting and destroying larger tumours.
However, individual tumour cells and small clusters of cancer cells can dodge treatment with lutetium-177, leading to a recurrence of the disease. This makes this form of radionuclide therapy unsuitable for lymphoma. In lymphoma, some of the tumour cells circulate in the bloodstream rather than forming a larger, localisable tumour.
Terbium-161 has a decisive advantage over lutetium-177: in addition to beta particles, it also emits conversion and Auger electrons. “This radiation has a range of less than one micrometre or one-thousandth of a millimetre. This is the size of a tumour cell,” explained Martin Béhé. Hence, terbium-161 acts on its immediate surroundings, making it particularly suitable for the targeted treatment of smaller tumours, providing a sense of reassurance about its safety and effectiveness.
“Terbium-161 fires more precise bullets, so to speak,” explained Elisa Rioja-Blanco, also from the Center for Radiopharmaceutical Sciences and first author of the study. Even individual cancer cells in the blood could be eliminated without causing severe side effects, offering hope about the potential effectiveness of terbium-161. “We can also catch small tumour foci that doctors may not even be aware of at the time.”
The isotope has a half-life of 6.9 days, which means that its effect is halved every 6.9 days. This is an advantage of radionuclide therapy: after manufacturing the drug, it can be transported to a hospital without losing a significant amount of its activity during transit. On the other hand, the radiation level decreases rapidly after treatment within a reasonable period.
Highly effective at killing cancer cells
In almost a third of all lymphoma patients, the tumour cells produce the CD30 receptor – in these patients, the new treatment could be applied. The same is true of T-cell lymphomas, in which the T-lymphocytes of the immune system become cancerous—a disease that has, until now, been difficult to treat.
The PSI researchers, led by Martin Béhé and Elisa Rioja-Blanco, produced the active substance, which consists of terbium-161 and an antibody against the CD30 receptor, at PSI.
They tested it in the laboratory on three types of cancer cells that produce CD30 receptors. They found that the substance was two to 43 times as effective at killing the cancer cells as the analogous substance using lutetium-177, depending on cell type. Further experiments showed that this is because the terbium-based drug caused more severe damage to the DNA in the cancer cell, which the cell itself is unable to repair.
The researchers then tested the drug on mice suffering from cancer. “This shows us where the substance accumulates in the body and whether it reaches tumours,” explained Elisa Rioja-Blanco. The tumour tissue and the mice that absorbed the terbium survived twice as long as their counterparts injected with a lutetium-177 drug. Some of the mice even ended up completely cancer-free after the treatment.
Preparing for human clinical trials
Terbium-161 is already being tested as an anti-cancer drug in several clinical trials – the PSI researchers have now, for the first time, scrutinised it as a potential treatment for lymphoma. “Our results are a good indication that the substance could also prove to be effective against lymphoma in humans,” said Elisa Rioja-Blanco.
