Diagnosis And Therapy

Later this year, a UK-based biotech company called Nuclide Therapeutics, is planning a clinical trial in lung cancer patients, a population with notoriously low overall survival rates.

“The symptoms don’t often show until the disease has spread, making surgery difficult, and the cancer develops therapy resistance at a rapid rate,” says Tim Witney, professor of molecular imaging at King’s College London, and the company’s co-founder & CSO.

The concept behind Nuclide Therapeutics’ trial is to use radionuclides in two stages. The first stage will see patients receive a diagnostic agent containing a harmless, low energy radionuclide simply designed to be detected on a medical scanner. This initial step is to determine whether the patient has treatment-resistant tumors, and if so, how many. Such information will then be used to guide the subsequent therapy with higher energy radionuclides, designed to kill the cancer cells.

“The amount of radionuclide therapy can be adjusted according to what the imaging scan shows us,” says Witney. “If there are multiple lesions that appear problematic, we can increase the radioactive dose, or if the patient is shown to have other complications, the dose can be dialed down.”

Esfahani perceives this kind of stratification as the future of the field. At Mass General Brigham, she is involved in trials where diagnostic radionuclides are being used to first examine whether a patient’s tumors carry biomarkers linked to more aggressive disease. “This way, we can say, ‘Okay, these patients are good candidates,’ before we put them through this heavy treatment,” she says.

More advances are likely to come, with companies developing ever more advanced homing molecules. For example, Swedish biotech Affibody has developed so-called ‘affibody molecules’ for delivering radionuclides to tumors that are roughly 1/20th the size of a traditional monoclonal antibody, allowing them to penetrate deeper into tissues.

Drug developers are also continuing to tweak the characteristics of radionuclides themselves to find the optimal combination. “We’re trying to get the radioactive molecule into the tumor, it has to stay there long enough to do damage, and then it has to leave the patient’s body as quickly as possible,” says Dominik Ruettinger, global head of research and early development oncology at Bayer Pharmaceuticals. “These are the three key steps and we’re still experimenting.”

While targeted radionuclide therapy is now predominantly used in patients where first-line treatments have already failed, there’s a possibility it could start to be trialed as an adjuvant or add-on therapy to existing treatments. In particular, the damage inflicted by radiation on cancer cells is known to increase their visibility to the immune system, suggesting that targeted radionuclides could work particularly well in combination with immunotherapy.

While Esfahani recommends caution, she feels that as evidence grows, these treatments could play an increasing role in cancer medicine.

“These are radioactive treatments that are being given systemically, so we should always be cautious about the toxicity of these drugs,” she says. “Because of this, a lot of regulatory agencies prefer that they are first tested in people who have failed other treatments. But once there’s data that shows, ‘Ok, this is safe and also as effective as standard treatments,’ then radiopharmaceuticals could be moved up as a first-line option where it’s the patient’s and physician’s choice about which treatment they want to receive.”

I look forward to watching these clinical trials carefully over the coming years—and one day, hopefully, welcoming a new standard tool into our toolbox for treating cancer.

Thank you to David Cox for additional research and reporting on this article.