A picture is worth a thousand words, they say. Especially if it is that of a PET (positron emission tomography), which shows the disappearance of metastases in men with very advanced prostate cancer, in which all treatments had now failed. But the words really do help to explain what those images mean: the era of radiopharmaceuticals has opened in the fight against cancer.
Let’s say right away that this is not a miracle cure that will heal everyone from prostate cancer or other cancers, but many argue that we are on the verge of a change in oncology. On the other hand, there must be a reason if, as Nature Biotechnology headlines, “Pharmaceuticals switch to nuclear power and continue to push radiopharmaceuticals”.
Prostate cancer, new investments in radiopharmaceuticals
What are radiopharmaceuticals?
Put simply, radiopharmaceuticals are radioactive atoms – or, better, isotopes – bound to molecules capable of recognizing cancer cells. Once administered, these isotopes reveal metastases and release their small lethal dose of radiation there – ultra-targeted and with manageable side effects.
From the thyroid to the prostate
To date, this strategy has been used successfully in less frequent neuroendocrine tumors, such as those of the thyroid gland. Now, for the first time, a radiopharmaceutical has been shown to be effective against prostate cancer – the most common among men – in a large clinical trial.
“One of the greatest successes in the history of nuclear medicine”, he defines it Johannes Czernin of the University of California at Los Angeles and editor of the Journal of Nuclear Medicine. The “Vision” study led by Memorial Sloan Kettering Cancer Center in New York and presented at the American Society of Clinical Oncology (ASCO) congress, demonstrated that a radiopharmaceutical can delay the progression of the disease and increase survival in patients with very advanced prostate cancer and who no longer respond to hormonal therapies.
ASCO 2021
Prostate cancer, new hope from nuclear medicine
by Tiziana Moriconi
The radiopharmaceutical in question uses the isotopes of Lutetium 177, transported by a receptor capable of binding to Psma, the membrane antigen of the prostate: a protein present in almost all prostate cancers and almost exclusively on cancer cells (and in very few other healthy areas, which limits side effects).
Once it reaches its target, Lutetium 177 decays, emitting high-energy electrons (beta particles), which break the cancer cell’s DNA and cause it to die.
Several new drugs have been approved in recent years for advanced prostate cancer that have allowed increased survival, but for the first time a mechanism other than that linked to androgens is exploited. According to Nature Biotechnology, Novartis – which developed the new radiopharmaceutical – has launched two more studies in patients with earlier-stage prostate cancer, and there are at least seven other radiopharmaceuticals using PSMA already in trials. Other big names investing in the sector include Bayer and AstraZeneca. “The industry orients its investments on the basis of strong scientific evidence,” he comments Sergio Baldari, professor of nuclear medicine at the University of Messina.
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Prostate cancer: “nuclear therapy” improves the quality of life
Results unthinkable until a few years ago
Yes, Psma has been a protein that has been known for more than 30 years, but it is thanks to the amount of new knowledge on cancer biology, tumor microenvironment and markers that such significant results have been achieved. And we have a capacity to produce molecules that was unthinkable until a few years ago. “Lutetium – continues Baldari – is not the only possibility: new radiopharmaceuticals exploit other radioisotopes, such as radium 223, actinium-225 and thorium-227, which emit alpha particles. They are heavy particles and act as a sort of nano-scalpels, more powerful than beta particles and potentially less toxic, since they bind specifically to the tumor tissue and carry out the radiant action, penetrating only a few tens of microns. In this way healthy tissues are substantially spared “.
Prostate cancer: + 3% of new cases per year among the under 50s
Possible developments in the therapy of other types of tumors
On the horizon there is therefore a new generation of radiopharmaceuticals that bind to target molecules present on various tumors. “For example – underlines the expert – there are clinical studies that test this approach in tumors of the head-neck, lung, bladder, breast, and blood cancers, such as myeloma and leukemia”. In short, there will be more and more nuclear therapy. Which is targeted and which can be customized.
Let’s go back to prostate cancer: Psma is first marked with a diagnostic radioisotope, gallium 68, which by means of a Pet exam detects in each patient whether, where and how much the radiopharmaceutical will be absorbed, both in the tumor and in the healthy tissue. “In this way – explains Baldari – we can select for therapy only those who have the appropriate characteristics and at the same time predict efficacy and possible toxicity. Instead of observing it on a single sample taken by biopsy or in surgery, we do it on the whole disease, with total body images. This will be the future “.
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