Bind precisely to tumor cells in order to target them with therapeutic radiation and cause their death.
This is the strategy used by radioligand therapy, an exemplary approach of precision and personalized medicine: precise because it specifically targets diseased cells, personalized because each patient receives a specially prepared drug and for which an organizational chain is activated that guarantees delivery to the patient within 72 hours of production.
An innovation, this one of radioligand therapy, which was born in Italy from the research carried out by Stefano Buono who, in 2002, founded a start up to bring to an industrial scale a patent developed during the years spent at CERN.
It is Advanced Accelerator Applications (AAA), part of the Novartis Group, a pioneer in the field of nuclear and precision medicine, which developed the first therapies with radiopharmaceuticals based on Lutetium 177 and which therefore positions itself as a pioneer of a new and effective therapeutic tool against cancer, still the second cause of death in the world.
“Radioligand therapy is a precision nuclear therapy,” he explains. Marco Maccauro, head of the simple structure of Nuclear Medical Therapy and Endocrinology of the National Cancer Institute of Milan - characterized by the use of radiopharmaceuticals consisting of radionuclides linked to some ligands that have specific characteristics for some tumors".
In fact, ligands "are able to recognize tumors because they bind specifically to receptors present on these tumor cells. Thanks to this ligand-receptor mechanism we have the therapeutic effect if the radionuclide is used for therapy, or diagnostic if one is used for diagnosis".
A dual use, therefore, both in the therapeutic and diagnostic phase, which in the near future promises to be extended to "other types of tumors, such as breast, pancreatic or other solid tumors".
Among the main features of radioligand therapy is the possibility of personalising the treatment. In fact, each patient receives a drug prepared specifically for it and for which an organisational chain is activated that guarantees its delivery within 72 hours of production.
According to Marcello Tucci, director of the Oncology unit of the ASL of Asti, "radioligand therapy is the opening of a stage towards the personalization of treatment, also for prostate cancer. In fact, the approval in Europe of the first radioligand-based therapy for the treatment of metastatic castration-resistant prostate cancer, progressive and PSMA-positive.
Tucci then explains that "today we know that molecular biology has provided us with a greater understanding of the biological factors underlying the progression of the disease, but we also know that prostate cancer cells express a membrane antigen specific to the prostate, which can be a therapeutic target. Radioligand therapy has this antigen as its therapeutic target and can truly give rise to the new era of personalized treatment".
Among the peculiarities of this therapeutic innovation is also the possibility of intervening and destroying diseased cells in an extremely targeted manner. In fact, by acting on tumors located in areas that would otherwise be difficult to intervene on, the collateral effects and functional damage to surrounding structures are limited.
All of this opens up potential applications for other types of cancer, such as breast and lung cancer, and translates into a positive impact on the patient's quality of life, as well as on survival, as in the case of prostate cancer.
“We are talking about patients with prostate cancer who have already been treated with other types of therapies, therefore fragile patients,” he clarifies. Maria Laura De Cristofaro, President of Europa Uomo Italia Onlus.
“The approval in the EU of the first targeted radioligand therapy for advanced and metastatic prostate cancer represents a significant milestone for patients with cancer who until now had a limited number of treatments at this stage of the disease”. The reimbursement of this therapy in Italy is expected in 2024.
However, the use of this therapy poses numerous challenges. The first, according to De Cristofaro, is that of the multidisciplinary team that must take care of the patient. The use of radioligands, in fact, "requires an expansion of the specialties present within the multidisciplinary team, therefore of a doctor specialized in nuclear medicine who must communicate in particular with the oncologist.
For patients, the multidisciplinary team is fundamental because it is there that the most suitable treatment strategy for the patient is decided”.
Then there is the issue of production and logistics, both of which are subject to well-defined radioactive decay times, intrinsic to the very nature of the radiopharmaceutical, which impose rigorous production, transport and administration timescales.
“If we think about Amazon Prime, we share with them the efficiency in sending drugs to our patients' beds and we share a daily fight against time, because we manage radiopharmaceuticals that have an extremely limited half-life - he explains Fabrizio Celia, Radio Pharmaceutical Country Operation Head AAA-.
So we have a production, supply chain, logistics and customer service model that is extremely close to the patient's bedside because the half-life of the therapy is only 72 hours. This means that when we receive an order request for a vial, once it is ready it must be injected into the patient's veins within 72 hours, whether they are in Italy, Japan or the United States."
“We then have another challenge,” adds Celia. “We like to call ourselves the ‘Tesla of pharmaceuticals’: what we have learned from the world of electric mobility is that being pioneers and having the best technology is not enough if this introduction of innovation on the market is not followed by an infrastructural adaptation.”
Article published on March 9, 2023 - 17pm
