Nuclear Medicine: technological advances and projects to combat the scarcity of radiopharmaceuticals

In october of this year, the Ministry of Science, Technology and Innovation (MCTI) and the Financier of Studies and Projects (Finep) announced that R$ 243 million was finally released to begin construction of Brazilian Multipurpose Reactor (RMB).

The news comes in the midst of a heating up in the nuclear medicine segment in Brazil and raises expectations regarding the possibility of a scenario in which the country will have the autonomy to meet its own demands.

The idea is that the RMB become one of the main nuclear technology research centers in Brazil - which includes the development of equipment for the health sector. In the words of Minister Luciana Santos, the reactor “will enable our country's autonomy in the production of radioisotopes, used in the manufacture of drugs for cancer treatment. Thus, we will reduce the risks of shortages, reduce costs and have better conditions to serve the population”.

Although nuclear technologies are more associated with imaging tests for the diagnosis of cancer, these resources are also used to detect and treat conditions in other areas, such as cardiology, neurology, oncology, thyroid, lymphoma, bone metastasis and endocrine tumor.

The concept of nuclear medicine

According to the definition of the National Institute for Biomedical Imaging and Bioengineering, founded at the National Institutes of Health (NIH), of the United States, nuclear medicine “is a medical specialty that uses radioactive tracers to evaluate body functions, diagnose and treat diseases”.

In this segment, the main examples of diagnostic technology are single-photon emission computed tomography (SPECT) and positron emission tomography (PET Scans).

SPECT — SPECT imaging equipment provides three-dimensional images of the distribution of radioactive tracer molecules that have been introduced into the patient's body. To generate computerized 3D images, gamma-camera detectors capture gamma-ray emissions, emitted by tracers injected into the patient.

PET — Positron emission tomography, on the other hand, also uses radiopharmaceuticals to create three-dimensional images. However, the main difference between SPECT and PET is the type of radiotracers used. While SPECT scans measure gamma rays, PET produces tiny particles called positrons.

For a better understanding of the topic, consider that a positron It is a particle similar to an electron, but with a positive charge. When a positron encounters an electron in the body, both annihilate each other and release energy in the form of two photons, which move in opposite directions. The positron emission tomograph detects these photons and, with this information, creates detailed images of the internal organs.

Among other important definitions, there are also the radiotracers or radiopharmaceuticals, substances that contain radioactive atoms and emit detectable radiation. They are administered to the patient and accumulate in specific organs or structures in the body, allowing problem areas to be viewed on imaging tests. In other words, in addition to facilitating diagnosis, it also helps in the monitoring of diseases and, sometimes, in therapeutic treatments.

Within this classification, a summary published in Remecs Magazine in 2018, highlights that the most used radiopharmaceuticals in Brazil are:

• Technetium 99 — the most used in Brazil, is necessary for scintigraphy to detect anomalies in the functioning of organs, such as the heart, kidneys and thyroid, due to its short half-life and versatility.
• Fluorine 18 — widely used in positron emission tomography (PET), being one of the most common for the detection of cancer and assessment of metabolic activities in tissues. The most popular substance with F-18 is fluorodeoxyglucose (FDG), which helps assess the consumption of glucose by cells, which is often high in cancer cells.
• Xenon 133 — used in pulmonary ventilation tests, as it allows evaluating the respiratory function of the lungs. It helps in the diagnosis of diseases such as emphysema and pulmonary embolism.
• Iodine 123 — used for thyroid scintigraphy and the diagnosis of hyperthyroidism. The combination of a shorter half-life and lower radiation emission make it useful for examinations without therapeutic purposes.
• Thallium 201 — used in myocardial scintigraphy, it helps assess heart blood flow and identify areas with possible irrigation problems. It is especially useful in patients with suspected coronary heart disease.
• Iodine 131 — it has both diagnostic and therapeutic applications, especially in the treatment of thyroid cancer and hyperthyroidism, as I-131 is absorbed by thyroid tissue and emits radiation that destroys affected cells.
• Gallius 67 — often used to identify lymphomas, infections and fevers of unknown origin, gallium accumulates in inflammatory tissues or tumors, allowing monitoring of disease activity.
• Krypton 81 — used in pulmonary ventilation tests. It is similar to xenon 133, but with properties that allow for fast, high-resolution respiratory imaging, which is ideal for diagnosing acute respiratory problems.

The threat of scarcity

The World Health Organization (WHO) estimates that by 2050, the incidence of cancer cases will increase by 77% - when compared to the numbers of 2022, the year in which more than 20 million cases were registered.

Considering that the main resources for the diagnosis and treatment of cancers are nuclear medicine equipment, this segment is expected to be under pressure in the future. Currently, according to the Brazilian Society for Nuclear Medicine (SBMN), about 2 million brazilians rely on nuclear medicine technologies to perform health tests and treatments. In practice, there are about 9 thousand procedures performed daily.

However, the supply to meet current demand is already a concern in several countries. In this sense, the crisis is mainly associated with the scarcity of raw materials for radiopharmaceutical production.

For example, as pointed out by BBC, after the stoppage of radioisotope production in the Netherlands in october of this year, the United Kingdom found itself short of raw materials, which delayed the carrying out of several tests for the diagnosis of cancer. The scenario worries families and specialists, since the sooner a treatment is started, the more likely it is that the disease will go into remission.

In 2021, a similar situation struck Brazil. At that time, the Institute for Energy and Nuclear Research had to completely stop producing radiopharmaceuticals for ten days, due to the difficulty of importing radioisotopes, according to Report from Revista Pesquisa FAPESP.

The Brazilian Multipurpose Reactor

Although approved in 2008, the construction of Brazilian Multipurpose Reactor (RMB) only gained speed recently. One of the main drivers was the restructuring of the PAC (Growth Acceleration Program), announced in september 2023, which, with the changes, now encompasses projects in the areas of science, health, education, digital inclusion and energy transition.

Altogether, the PAC is expected to generate R$ 240 billion in investments. However, with private sector participation, the government aims to reach R$ 1 trillion over the next four years. Of this amount, around R$ 2.5 billion is expected to be allocated to the RMB, with an estimated R$ 1 billion expected to be invested by 2026.

According to a FGV Energia study, in collaboration with the Brazilian Association for the Development of Nuclear Activities (Abdan) and Eletronuclear, medicine is the second largest area to use nuclear technology in Brazil. As the analysis highlights, there are about 60 procedures performed in more than 400 services spread across the country.

The country currently depends on foreign suppliers to meet the demands for radioisotopes in hospitals and clinics. One of the most sought after is Molybdenum-99 — used in the production of Technetium-99 — as it is a radiopharmaceutical used in scintigraphy.

Thus, with its own reactor, Brazil should be able to fill the gap left by the Canadian reactor, which accounted for more than 40% of the world's demand for technetium-99.

Also according to the FGV study, the guarantee of stability in the supply of these inputs should generate annual savings of more than US$ 13 million in import costs.

In addition, by reducing international dependence, it will also be possible to consider expanding the supply of nuclear medicine services, such as increasing the number of clinics and hospitals that offer these treatments in the country. Expanding the supply of nuclear technologies would be especially beneficial for countries like Brazil. According to a study published in JAMA Network Open, by 2050 cancer mortality is expected to increase by 146% in low-income countries.

Among other promises, the RMB can still generate positive impacts on the labor market and the sector's economy. According to projections, by 2036, the number of direct jobs could triple - when compared to 2021 data -, reaching around 8.3 thousand jobs.

At the same time, it is expected that by 2036, the sector's revenue will exceed 535 million reais - when compared to the R$ 210 million seen in 2021 - and the number of procedures performed will exceed 3.6 million.

In addition to health benefits, the brazilian multipurpose reactor should also provide advances for national scientific research, as well as expand development capacity in fields such as nuclear physics and biomedicine.

Finally, following this line, the brazilian nuclear medicine has seen other advances this year, such as:

• Specific imaging test for prostate cancer — the Molecular Medicine Technology Center at UFMG held its first specific imaging test for prostate cancer using the 18F-PSMA marker.

• Unicamp inaugurates structure for the production of radiopharmaceuticals — the Hospital de Clínicas da Unicamp inaugurated a new radiopharmacy structure to produce specific radiopharmaceuticals for the diagnosis and treatment of cancer and other diseases. The facility includes equipment that allows the development of new molecules and reduces dependence on imports, especially important due to the short half-life of these compounds.

• Fiocruz and University of Coimbra Partnership — the institutions entered into a agreement to develop radiopharmaceuticals in Brazil. In addition to seeking to register these products in the local market, the collaboration should make it possible to expand Farmanguinhos's portfolio of radioactive drugs, reduce costs, and strengthen SUS services. The partnership also includes an educational program to train qualified professionals.

• Nuclear medicine technique for studying Alzheimer's in people with Down syndrome — at the University of São Paulo (USP) researchers mapped the presence of neuroinflammation in people with down syndrome using nuclear medicine techniques. In the research, the presence of beta-amyloid plaque formed by amyloid peptide fragments, which are deposited between neurons causing inflammation and interrupting neural communication, was detected.