Radioligand therapy - Dr. Kust for Jutarnji list

Our oncologist Dr. Kust writes for Jutarnji list and Živim.hr about a new targeted approach in the fight against cancer. We are publishing the article in its entirety, and you can read the original at the link.

Radioligand therapy: a precise weapon in the fight against cancer

The world of oncology is constantly looking for ways to increase the effectiveness of treatment, while at the same time reducing side effects and preserving the quality of life of patients. One of the newer and most promising approaches in this direction is radioligand therapy (RLT) – a form of targeted treatment that uses radioactive molecules to precisely target tumor cells, while bypassing healthy tissue. Although this term is not yet widely known in Croatia, the number of patients receiving this therapy is constantly growing, and its results give hope for the treatment of even those forms of cancer that have so far been extremely resistant to standard methods.

What is radioligand therapy?

Radioligand therapy is a combination of nuclear medicine and molecular oncology. It is based on the idea that a radioactive compound - an isotope (e.g. lutetium-177 or actinium-225) is bound to a so-called ligand - a small molecule that has the ability to recognize and bind to specific binding sites - receptors on the surface of tumor cells. After such a complex (radioactive ligand) is intravenously introduced into the body, it travels in a targeted manner to the site where the tumor cells are located and releases localized radiation there, thereby destroying the malignant tissue.

Unlike classical chemotherapy, which acts systemically and often causes serious side effects, RLT acts precisely, localized and selectively, significantly reducing damage to healthy cells.

How exactly does it work?

For RLT to be possible, the tumor must express a specific receptor that can be "recognized". The most known examples are:

• Somatostatin receptors – expressed in neuroendocrine tumors (NET)

• PSMA (prostate-specific membrane antigen) – in prostate cancer

A ligand (most often a peptide or an antibody) is a molecule that specifically binds to that receptor. When the ligand is labeled with a radioactive isotope, a medicine is obtained - a radiopharmaceutical, which is transported to the tumor via the bloodstream. There it binds to the receptor, and radiation (most often beta or alpha particles) damages the DNA of the tumor cell and leads to its death (Figure 1).

Figure 1. Mechanism of action of radioligand therapy.

In what cases is it used?

Currently, the most common are:

1. Neuroendocrine tumors (NET)

Therapy: Lutetium-177 DOTATATE (commercially known as Lutathera®)

Indication: metastatic NET with expressed somatostatin receptors

Approved by EMA and FDA

The NETTER-1 study showed a significant increase in time to progression compared to standard therapy (median 28.4 vs 8.5 months)

2. Prostate cancer

Therapy: Lutetium-177 PSMA-617 (commercially: Pluvicto®)

Indication: metastatic, late-stage disease, refractory to hormonal therapy

Approved in the EU in 2022

The pivotal VISION study showed a significant prolongation of survival: overall survival was 15.3 vs 11.3 months in favor of RLT

What does the therapy look like in practice?

Radioligand therapy is performed in specialized nuclear medicine centers, usually in a hospital setting. The patient receives the drug via infusion, after which he remains in isolation for several hours (or until the next day) due to the low level of radioactivity (Figure 2).

The therapy is usually performed in multiple cycles – usually 3 to 6, spaced several weeks apart. After each cycle, the disease response is monitored using laboratory findings and imaging methods (e.g. PET/CT).

Figure 2. Radioligand therapy – the path through the bloodstream to the tumor.

Are the side effects mild?

Compared to classic chemotherapy, radioligand therapy has less pronounced side effects. The most common are:

• Fatigue

• Mild nausea

• Temporary drop in blood cells (leukocytes, platelets)

• Dry mouth (especially with PSMA therapy, because salivary glands express PSMA)

More serious side effects are rare, but kidney and bone marrow function are carefully monitored during treatment.

Patient experiences

Mr. Marc (64), suffering from metastatic prostate cancer, shared his experience online: “After three cycles of Lutetium, my tumor values ​​have dropped more than ever before. I feel better, more energetic and have not had any severe side effects. I had already lost hope, and now I am planning a vacation again.”

Similar experiences are also recorded by patients with neuroendocrine tumors, who often report improved appetite, energy and reduced pain after the first cycles of therapy. It is important to note that the patient must have a positive PET scan (DOTATATE or PSMA) and meet certain criteria. Specialist doctors decide on the suitability of the therapy as part of a multidisciplinary oncology team.

What does the future hold?

Radioligand therapy is only at the beginning of its development. New targets (receptors) and new radionuclides are being investigated, including actinium-225, which emits alpha particles with an even stronger local effect. Trials are underway for:

• Breast cancer (HER2 positive)

• Glioblastoma

• Bladder cancer

• Lymphoma

The combination of RLT with immunotherapy is also being investigated, which would further enhance its effectiveness.

Conclusion

Radioligand therapy represents a new chapter in the treatment of oncological diseases. It combines molecular precision with the therapeutic power of radioactive radiation – targeted, effective and with minimal side effects. For some patients for whom other options have been exhausted, RLT brings new hope and real clinical benefit. In some cases, it can be a key change in the treatment path.

Related articles:

Neuroendokrini tumori

Rak prostate

Do you need more information about this topic? Contact us.