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Nuclear medicine

In the crystal’s target

Probe detects tumors and assists with surgeries

In appearance the crystal of thallium bromide reminds one of amber-yellow, the beautiful fossil resin coming from extinct pre-historic pine trees. The resemblance, however, is merely apparent, since the crystal developed at the Nuclear and Energy Research Institute – IPEN, when placed on the tip of a surgical probe, helps the surgeon in precision cutting of the tissue affected by cancerous cells and in the identification of lymph nodes – the points of confluence of the lymphatic system – during surgery. The lymphatic veins make up part of the circulatory system of the human body and distribute fluids such as water and cells. In the surgical procedure it is necessary to inject, between two and twenty four hours previously, a radioactive substance into the location of the tumor, such as the radioactive substance technetium-99. “The radioactive substance emits gamma radiation, which is captured by the probe”, explains professor Renato Santos de Oliveira Filho, from the discipline of Plastic Surgery of the Federal University of Sao Paulo (UNIFESP), who is going to coordinate the clinical studies with the new probe. Other applications for the thallium bromide crystal are being studies by the IPEN researchers for its use in industry as a controller of paper or plastic sheeting thickness, for example, and in astrophysics as cosmic trackers of X-ray emissions.

The major nuclear medical centers in the country make use of radioactive guided probes made from other crystals, such as cesium iodide and cadmium telluride, but they are imported and cost between US$ 20,000 and US$ 40,000. The estimation is that the price of the thallium bromide probe developed at IPEN will be around US$ 6,000, and will have the same quality. “The high price of imported equipment and the lack of technical assistance were the motives that led to some doctors and IPEN personnel to look towards the development of a national probe”, says the research coordinator, Margarida Mizue Hamada, from the Radiation Sensor Development Laboratory at IPEN. Various groups in the area of crystal growth and the preparation and description of these materials as radiation detectors with diverse applications are working in the laboratory.

Perfect crystals
Crystals of silicon and germanium are recognized as excellent semiconductor detectors of radiation, but need very low temperatures in order to function. For this reason the researchers involved in the project decided to work with a semiconductor crystal of thallium bromide, which functions at room temperature. To make the crystals grow with perfection was a challenge transposed with the development of a new methodology for the purification of the salt of thallium bromide. The first stage in this process involves placing the salt in a tube of sealed quartz, which goes into the furnace at a temperature of between 500oC and 555°C, for the purification of the material through a process called zonal refining. “Purity is the determining factor in the quality of the crystal in order to act as a radiation detector with high energy resolution”, says Margarida. Next the material goes to another furnace for the growth of the crystal. Afterwards the crystal is cut into slices of different thicknesses using a diamond saw and then the slices are polished. Electrical contacts are placed on these slices so that they function as radiation detectors.

The radiation emitted by the radioactive medicine injected into the organism excites the radiation detector and produces a small electrical signal. This signal is amplified, quantified and transformed into a sonorous signal in order to guide the surgeon to the location of the affected area without having to resort to visual monitoring. The probe is encapsulated into a cylindrical mounting of stainless steel in order to guarantee asepsis. Connected to an electronic counting unit – a metallic box – and linked onto a computer, it shows the measure of radiation in each point of the tumor. The technique of using a radioactive guided surgical probe, which has spread worldwide over the last decade, has been in use in various Brazilian hospitals.

The evaluation is done starting from the sentinel lymph node, the first to receive drainage from the lymphatic network. “The method shows high efficiency in the identification of hidden metastases in the tumors of initial dissemination preferentially by way of the lymphatic, such as in skin melanoma and in breast cancer”, says Oliveira Filho. “The major advantage of this technique is to minimize surgical intervention, because only all of the lymph node chain will be removed if there has been effective compromising.” For now it has been used principally for melanomas and breast cancer. Experimental studies are being conducted to extend this technique to other types of tumor.

In the project funded by FAPESP two surgical probe prototypes were developed. One of them made use of the technology of semiconductor detectors using thallium bromide and the other scintillation detectors using cesium iodide doped with thallium. The two prototypes have shown good results. The major advantage in the use of thallium bromide is that it is not necessary to have a photosensitive component (photodiode) in order to convert the light into an electronic signal, while the cesium iodide needs this material, classified on the list of nuclear applications, and therefore with restrictions in order to obtain it. And what turns the use of thallium bromide more advantageous when compared to cadmium telluride is that the crystal possesses a high atomic mass number and consequently high electron density in the crystalline network. This yields high efficiency in the production of charge in the interior of the detector due to the increase in probability of an interaction of radiation with the detector’s material medium. In this manner, even crystals that are very small are sufficient to interact with the injected radioactive medicine. This makes a reduction in the dimensions of the radioactive guided probe possible, turning it easier to be managed by the surgeons.

The methodology for the purification and crystal growth of thallium bromide was the theme of a doctoral thesis by Icimone Braga de Oliveira, supervised by professor Margarida and also financed through FAPESP. All of the technology to create the electronic part of the crystal system, the processing module, the radiation counter, the exhibition and sound  alarm system make up part of the doctoral thesis by Fábio Eduardo da Costa. “The technical tests, which preceded the clinical studies, have shown that the thallium bromide probe shows the same physical characteristics of the other probes that exist on the market”, says Oliveira Filho.

The implementation at IPEN of the technology for scintillation crystal growing and their characterization as radiation detectors began in 1992 with the arrival of the visiting professor Shinzou Kubota, from the Rikkyo University in Japan, for a period of four months with financial help from the Foundation. Today the institute provides crystals for various applications, such as detectors for measuring traces of mercury in aquatic marine organisms and for detecting radiation of cosmic origin. With the development of the thallium bromide probe, the IPEN is responding to a professional demand and hopes to contribute with a new technology for disseminating the use of a radioactive guided probe in oncology surgeries. The prototype that will be used at UNIFESP was produced by the institute, but as soon as the clinical tests have been carried out the technology should be passed on to the companies that have shown interest in the industrial production of the probe.

The project
Development of a semiconductor crystal of thallium bromide for application as a radiation detector and scintillation spectrometer
Regular Line of Research Assistance
Margarida Mizue Hamada – IPEN
R$ 93,783.75 (FAPESP)