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NUCLEAR MEDICINE

Radiation instrument

The Brazilian Multipurpose Reactor should be able to meet Brazil’s needs for radiopharmaceuticals to diagnose and treat disease

Tomography done with application of technetium-99m in patient shows cancer in the upper leg bones

LATINSTOCK / SIMON FRASER/MEDICAL PHYSICS, RVI, NEWCASTLE UPON-TYNE / SCIENCE PHOTO LIBRARY/SPL DCTomography done with application of technetium-99m in patient shows cancer in the upper leg bonesLATINSTOCK / SIMON FRASER/MEDICAL PHYSICS, RVI, NEWCASTLE UPON-TYNE / SCIENCE PHOTO LIBRARY/SPL DC

If all goes as planned and budgetary resources remain available, within five years Brazil will become self-sufficient in producing radioisotopes—radioactive substances that can be used to diagnose and treat various diseases, as well as for industrial, agricultural and environmental applications. The Brazilian government is expected to invest about $500 million, equivalent to approximately R$1.09 billion, in constructing the Brazilian Multipurpose Reactor, a major research center to be built in the city of Iperó, located in the Sorocaba region, 130 kilometers from São Paulo.

Construction of the project is one of the goals of the Ministry of Science, Technology and Innovation (MCTI) and is aligned with the Brazilian Nuclear Program (BNP). “In addition to producing radioisotopes for health, industrial and agricultural applications, the Multipurpose Reactor will test fuel and structural materials for nuclear centers,” says José Augusto Perrotta, the project’s technical coordinator; he also serves as an advisor to the head of the National Nuclear Energy Commission (CNEN), an agency of the Ministry and responsible for the Reactor. “The reactor will also provide neutron beams for scientific and technological research and educate and train professionals to meet the needs of the BNP.”

Among the most important products of the new Brazilian research reactor will be the radioisotope molybdenum-99 (Mo99), which is produced from the fission of uranium-235 (U235). Along with Mo99, a device called a technetium generator is also being built. Technetium-99m (Tc99m, the m stands for metastable) is a radioisotope and forms the basis of radiopharmaceuticals used in about 80% of the diagnostic procedures in nuclear medicine.

In Brazil, about 2 million procedures in this medical area are performed each year. “Brazil needs to import all its molybdenum-99 needs,” says Perrotta. “In 2013, around 21,000 curies [a curie (Ci) is the unit used to measure radioactivity] of Mo99 were imported, at a total cost of $10.1 million.” According to Perrotta, the Multipurpose Reactor is expected to produce at least one thousand curies per week of molybdenum-99, which is equal to approximately 50,000 curies per annum.

078-081_Reator Ipen_221Today the world has between 240 and 250 nuclear research reactors in operation, and some are producing radioisotopes for many diverse applications. For nuclear medicine, Canada alone accounts for 40% of the world’s production. When, in 2009, the main Canadian reactor encountered problems and was temporarily shut down, there was a huge drop in supply, which led to a crisis in this area of medicine. The problem may become more acute within a few years because most reactors in operation are near the end of their useful lives and will be deactivated.

The Multipurpose Reactor and its associated laboratories—for processing radioisotopes, analyzing irradiated materials and neutron beams—will be located in an area of 2 million square meters (m2), adjacent to the Aramar Experimental Center of the Brazilian Navy, which transferred 1.2 million m2 of land for the reactor. Another 800,000 m2 will be expropriated by the São Paulo state government and also assigned to the project.

As for the reactor itself, Perrotta says it will be an open-pool type, in which water is used as a neutron moderator, radiation shielding and cooling to remove the heat generated by nuclear reactions. “The water keeps the reactor’s temperature below 100°C, which provides greater safety for the system,” says Perrotta. “This type of reactor is simpler than those used in nuclear power plants. The degree of safety and reliability is higher, which means they can be located at research centers and universities near cities.”

Technetium-99m is injected into the patient for purposes of the diagnosis. Tomography equipment captures the tracer images of the radiopharmaceutical

CUSTON MEDICAL STOCK PHOTO / SCIENCE PHOTO LIBARYTechnetium-99m is injected into the patient for purposes of the diagnosis. Tomography equipment captures the tracer images of the radiopharmaceuticalCUSTON MEDICAL STOCK PHOTO / SCIENCE PHOTO LIBARY

The new reactor will have a thermal power of up to 30 MW, which in terms of size in the world puts it in the intermediate range. “The reactor uses as a point of reference the design of the Open Pool Australian Lightwater (OPAL) reactor, which has a capacity of 20 MW and opened in 2007,” says Perrotta. “The basic design of our reactor was developed cooperatively by CNEN and its counterpart in Argentina, the National Atomic Energy Commission (CNEA). The Argentine company Invap was hired to do this, because it built the one in Australia.” CNEA is also building a reactor similar to our Multipurpose Reactor, and this cooperation helps to reduce costs for both parties. Intertechne, a Brazilian company, was hired to do the basic engineering and infrastructure design for housing the Brazilian reactor and its laboratories and associated systems.

The National Science and Technology Development Fund (FNDCT) has allocated R$50 million for the basic engineering design; it forms a reserve fund that finances research, development and innovation and is administered by the Brazilian Innovation Agency (Finep), which is linked to the Ministry (MCTI). In addition to the basic design, a number of studies and reports on environmental impacts and license applications are needed for construction of the Multipurpose Reactor; CNEN has invested R$2.7 million of its budget in this regard.

Producing Mo99 in the reactor includes a series of steps that are inherent to the nuclear fuel cycle. “The ore is removed from the mine and processed to yield a concentrate of uranium known as yellowcake,” says Perrotta. The process to be followed, which involves technology Brazil has already mastered, is carried out in several phases and results in small plates, known as targets, which contain enriched uranium dispersed inside.

The targets are irradiated in the reactor for one week to produce radioactive elements from the uranium fission, among them Mo99. These targets are then dissolved in the processing laboratory, producing a high-purity solution of Mo99, which is sent to the radiopharmacy producing radiopharmaceuticals. A device known as a technetium generator is produced there.

This technetium generator is distributed to hospitals and clinics. “Using the technetium generator, a medical specialist is able to extract calibrated solutions containing technetium-99m that, associated with specific organic molecules, are used for diagnostic nuclear medicine,” says Perrotta.

Different uses
To do this, the physician injects this solution, which, according to the patient’s physiology, based on affinities to and rejections of various types of cells, goes to the organ or region to be diagnosed. How a diagnosis is done with nuclear medicine is different from one that uses X-rays, in which radiation passes through the patient without leaving any traces and sensitizes a photographic film. Technetium-99m emits gamma radiation. After the patient is injected with the solution, radiation begins to be emitted from within the patient’s body, which is captured externally by radiation detectors.

Dr. Celso Dario Ramos, president of the Brazilian Society of Nuclear Medicine (SBMN), says that radioisotopes, such as technetium-99m, are key to the diagnosis of many diseases. Other radioisotopes, such as iodine-131 and lutetium-177, which will also be produced in the Multipurpose Reactor, enable the treatment of various other diseases, such as thyroid cancer and neuroendocrine tumors. “With technetium-99m it is possible to make images that allow us to see cellular metabolism in living tissue,” he says. “With the various radiopharmaceuticals it is possible to see the distribution of a particular hormone in the body or glucose uptake in a region, which can reveal the presence and aggressiveness of a tumor, for example. Radiopharmaceuticals even make it possible to see the functioning of internal organs, such as bones, the lungs, heart, brain, liver and kidneys.”

Technetium-99m has an additional advantage: a short half-life. Half-life is the time it takes for a radioactive element to lose (emitted in the form of radiation) half of its atoms. “Uranium-235, for example, has a half-life of 700 million years and cesium-137, 30.2 years,” says Perrotta. “Iodine-131, another element used in nuclear medicine and that will also be produced in the reactor, has a half-life of 8.02 days and that of technetium-99m is only six hours. That is to say, every six hours the intensity of radiation in the patient’s body is reduced by half, and in two or three days there will be virtually no radioactive intensity remaining.”

The high-intensity neutron flux generated in the Multipurpose Reactor will test fuels and materials used in reactors for power generation, such as at the Angra dos Reis nuclear power plant (Rio de Janeiro State) and for propulsion, such as the method that will be used in the prototype nuclear submarine being developed by the Navy. “The reactor will provide technical insurance to these projects, ensuring the continued development of nuclear knowledge for Brazil,” says Perrotta. “Finally, it will house a laboratory using neutron beams in materials research, complementing the work of the National Synchrotron Light Laboratory (LNLS), based in Campinas, São Paulo State. If we do not move forward in this industry, we will end up on the margins of world development and be at the mercy of foreign suppliers.”

And so Dr. Ramos, who is also director of the University of Campinas (Unicamp) Nuclear Medicine Service believes it is “extremely important” for Brazil to build the reactor. “The impact will not only be in nuclear medicine, but also in physics, chemistry, engineering, biology and other areas of research,” he says. “The reactor will not just produce radioisotopes. It will be a major research center, equal in importance to the LNLS.”

According to Perrotta, the Multipurpose Reactor will help the region where it will be located to become a center for nuclear technology in Brazil.

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