Professor Niklaus Schaefer started working in nuclear medicine in 2008, long before this relatively new field of medicine became fashionable. Since then, he and his team at the CHUV have treated over a thousand patients with radioligand therapy, an incredibly complex and delicate form of treatment. Niklaus explained to us how radioisotopes can be harnessed to develop personalised medicine in oncology and why it’s a promising therapy.

What is radioligand therapy?

Radioligand therapy (RLT) is an advanced nuclear medicine procedure used to treat specific types of cancers. The two key components in RLT are targeting ligands and radioisotopes. It works by combining the ligand, a molecule that binds to identified cancer cells in the body, with the radioisotope, a radioactive moiety that destroys the target tissue. Because the ligand selectively attaches to targeted cells, the internal irradiation from the therapeutic isotope can be delivered precisely to specific tumour tissue. Consequently, it can eliminate cancer cells while sparing the surrounding healthy tissue, making the treatment highly localised and effective.

RLT is used in diagnosis and therapy. How different is its use in each?

RLT is a form of antitumour therapy that uses internal, local irradiation to destroy cancer cells. RLT is guided by diagnostic imaging: the same ligand is attached to a diagnostic isotope to delineate and quantify the target tumours within the body. Therefore, diagnostic and therapeutic radioligands complete each other, using the same vector to measure and treat the disease. This principle is called theranostics or, more specifically, radiotheranostics.

When is RLT used?

RLT can be used for any cancer where either the tumour cells or cells of the tumour microenvironment feature a specific structure (i.e. a receptor) that can be targeted by its complementary radioligand. For prostate cancer, the prostate-specific membrane antigen (PSMA) receptor can be specifically targeted by the PSMA inhibitor radioligand. Alongside other researchers, we are currently trying to expand this concept to other types of cancer, such as glioblastoma (an aggressive brain tumour), soft tissue sarcoma and breast cancer.

Because RLT is a relatively new field, right now it’s mostly used for patients with advanced cancers, where more common forms of therapy – such as classical chemotherapy – have failed. That said, as the field progresses and an increasing number of clinical trials show the value of RLT, it is being used earlier and earlier.

What are the advantages of RLT therapy?

Compared to other cancer treatments, like chemotherapy for instance, RLT is highly targeted. Since we use the theranostic principle (employing both a diagnostic and a therapeutic radioligand), we can visualise the disease prior to treatment. This helps us to personalise our approach, giving each patient the best outlook possible when going through RLT.

And because the treatment is highly targeted, patients hardly ever suffer from side effects like hair loss, nausea or relevant immune suppression. In the weeks between treatment cycles, patients are relatively autonomous and do not need regular check-ups with their local oncologists. This freedom is a major advantage of RLT, as it helps a patient to maintain their independence and quality of life.

Another benefit lies in the structure of the process: due to the diagnostic step prior to therapy, patients already understand what we are treating when treatment begins. We are even able to measure the distribution of the therapeutic activity by imaging after every cycle of therapy. The patient, together with the physician, can track the evolution of the disease and the effects of treatment. This visual, directly measurable component is profoundly different to any other cancer therapy.

Can RLT therapy be given to any kind of patients, regardless of their age?

Currently, RLT can only be given to patients with specific malignant diseases, like neuroendocrine tumours or hormone-resistant prostate cancer. But, because patients don’t suffer from pronounced side effects, RLT can be given to patients of any age group. The only stipulation is that patients must be physically independent, as they are hospitalised in specific radioprotection rooms.

Certainly, younger patients can benefit from this treatment, for example in cases of rare paediatric tumours. In these patients, however, we have to discuss the risk of developing a secondary malignancy because of the use of radiation. Still, it must be stated that this risk is associated with different treatment modalities for cancer, including chemotherapy or external beam irradiation.

How accessible is RLT today? 

Right now, RLT therapy comes with some challenges. As we’ve seen, it’s a personalised medicine that needs to be produced individually for each patient. It’s also a radioactive material that entails complex logistics, from transportation to storage.

To offer RLT, a hospital must put specific infrastructure and the right resources in place. It will need a radiopharmacy with appropriate storage for radioactive materials and treatment facilities specially designed to limit radioactive emissions and waste. Staff – from pharmacists to nurses – need specific training, while radioactive waste needs to be disposed of in a specific way.

All of this means that not many healthcare institutions can offer RLT. As things stand, CHUV is the only hospital to offer RLT in western Switzerland. In other words, for this type of therapy to reach as many patients as possible in the future, we will need some incredible teamwork, alongside significant effort and investment at all stages of the process.

Once it becomes more accessible, do you think RLT therapy will surpass other cancer treatments?

In many cases, chemotherapy or other forms of treatments are currently still the best choice for our patients. RLT is not always a better option per se, but it is a very useful option for specific patients with specific diseases. In many cases, cancer is still an incurable disease, and we are in urgent need of new treatment concepts. The more options and modalities we have, the better we can serve patients. I am convinced of the relevance of RLT, which has proven effective in several trials, but it should be seen as a valuable addition to the existing landscape, rather than as a competitor.

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