Radionuclide therapy with the radioactive element terbium could effectively combat lymphoma. This is demonstrated by promising results from experiments carried out at the Paul Scherrer Institute PSI in collaboration with Inselspital - Bern University Hospital. The team's findings are being published today in the Journal of Nuclear Medicine. The researchers are now refining this type of therapy in order to carry out clinical trials.
Every year, almost 2,000 people in Switzerland are diagnosed with lymphoma, and about 570 of them die from the disease. Researchers at PSI's Center for Radiopharmaceutical Sciences are now proposing a new therapy that could soon increase the chances of survival for many of those affected: radioimmunotherapy with the nuclide terbium-161.
"The radioactive isotope terbium-161 is attached to an antibody and injected into the bloodstream of the patient," explains 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 tumor to kill the cancer cells with its radioactive radiation." Healthy organs in the body are spared, on the other hand.
In almost a third of all lymphoma patients, the tumor 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.
Radiotherapy from within
Radionuclide therapy is already well established in clinical practice. Hospitals currently carry out this form of cancer treatment with a different radioactive substance: the nuclide lutetium-177. This is used to treat prostate cancer and tumors arising from hormone-producing cells. Radioactive lutetium decays to produce high-energy, high-velocity electrons, called beta particles, which combat larger tumors effectively.
However, individual tumor cells and small clusters of cancer cells elude treatment with lutetium-177 and can lead to a recurrence of the disease. This makes this form of radionuclide therapy unsuitable for lymphoma. In this type of cancer, some of the tumor cells circulate in the bloodstream rather than existing as a larger, localisable tumor.
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 tumor cell," explains Martin Béhé. Hence, terbium-161 acts on its immediate surroundings, making it particularly suitable for the targeted treatment of smaller tumors.
Terbium-161 fires more precise bullets, so to speak."
Elisa Rioja-Blanco, 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. "We can also catch small tumor 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 for radionuclide therapy: after manufacturing the drug, it can be transported to a hospital without losing too much of its activity on the way. On the other hand, the radiation level decreases rapidly after treatment within a reasonable period of time.
A powerful weapon against cancer cells
The PSI researchers led by Martin Béhé and Elisa Rioja-Blanco produced the active substance, consisting of terbium-161 and an antibody against the CD30 receptor, themselves at PSI. They then tested it in the laboratory on three types of cancer cells that produce CD30 receptors. They found that - depending on the type of cell - the substance was 2 to 43 times as effective at killing the cancer cells than the analogous substance using lutetium-177. Further experiments have shown 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 actually reaches tumors," explains Elisa Rioja-Blanco. The substance was indeed preferentially absorbed by the tumor tissue. On average, mice treated with terbium-161 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.
On the way to 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," says Elisa Rioja-Blanco. Clinical studies will hopefully soon show whether this is indeed the case.
The Lymphoma Challenge, organised by ETH Zurich, is providing financial support for the project. The team has now secured follow-on funding from Innosuisse to further investigate and optimise the drug so that it can be commercialized and tested in humans in the future.
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