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nuclear medicine

Ipen launches ultra-pure iodine -123

A radioactive isotope detects the presence of tumors and alterations in the thyroid gland

An essential resource of nuclear medicine for the diagnosis of a series of illnesses is now available in São Paulo. The Institute of Energy and Nuclear Research (Ipen), of the National Commission of Nuclear Energy (Cnem), has developed its own technology and has begun to produce ultra pure iodine -123, a radioactive isotope which, when used in specific examinations, facilitates the localization of tumors and alterations in the thyroid gland, in the heart and in the brain. In the form of a colorless liquid, this substance has a short half-life (the time in which its radioactivity falls by half) of 13 hours. This represents an advantage for the patient who is submitted to a small dose of this type of product, as well as being beneficial towards the precision and speed of the diagnosis.

By the beginning of next year, the product will be available to all hospitals and diagnostic centers who wish to have it. There is only a little way to go for this to happen. “We have still to settle the process. Only then can we produce on a totally commercial scale and establish a final price for the product”, informs  the physicist Valdir Sciani, coordinator of the Irradiation Group of the Cyclotron of Ipen. The cyclotron, model Cyclone 30, is an accelerator which cost close to US$ 5 million and produces proton beams for the production of radioactive isotopes which are of interest in medical diagnosis such as galium-67, thalium-201, indium-111, iodine-123 and fluorine-18. The development of this new product was possible as the assistant research project of FAPESP Development and Implantation of a Method of Obtaining Iodine-123 by the Irradiation of Xenon-124 at Ipen-Cnen, coordinated by Sciani. The financial support of the Foundation was R$ 109,000.00 and US$ 50,000.00. The International Atomic Energy Agency contributed US$ 50,000.00 and the contribution of the institute itself was of another R$ 70,000.00.

The methodology for the production of iodine-123 through the irradiation of the gas xenon is not new and is also used by the Institute of Nuclear Engineering (IEN), of Rio de Janeiro. In São Paulo, the system was entirely developed by Ipen. “The mastery of the technology made possible the development and the implementation of the correct systems for all the phases of the process, in an effort which took two years”, explains Sciani. The work also involved the participation of teams from the Cyclotron Laboratory of the Center of Radioactive Isotopes and of the Center of Radiation Technology of Ipen.

Besides the direct investments in the project, they also made use infrastructure investments, such as the acquisition of a magnetic distributor with five exits for one of the beams of protons of the Cyclone 30. With this, they can now have installed up to five irradiation chambers, one of them exclusively for the production of iodine-123. Before only one chamber could be used at a time and it had to be dismounted and remounted for each new radioactive isotope produced on line.

Iodine at Incor
The Heart Institute (Incor) of the University of São Paulo (USP) is one of the consumers of iodine-123. Cláudio Meneghetti, Director of the Service of Radioactive Isotopes for Incor, informs that the first use of iodine-123 will be in the study of the prognosis of patients who are on the heart transplant waiting list, to identify those who have the higher risk of death, through the use of a substance – methyliodobenzylguanidine – labelled with iodine-123. With this substance in the organism, the patient is subjected to an examination of scintillography in which a special machine captures the radiation concentrated in the sick areas in a manner similar to that of x-rays.

According to the pharmacologist Marycel Barboza, responsible at Ipen for marking the molecules with radioactive isotopes, iodine-123 is used only in diagnosis and in the monitoring of treatment, different from the use of iodine -131, used in diagnosis and radiotherapy. With the iodine-123, one can diagnose dysfunctions of the thyroid gland such as hypo and hyperthyroidism. Inserted into the methyliodobenzylguanidine, it makes it possible to carry out precise studies of myocardium and the identification of endocrine tumors and of neural crests (where central or peripheral nerves are involved), which are of low occurrence, but affect children – neuroblastomas – and young adults – pheochromocytoma. The union of the two substances also facilitates the therapeutic follow up, correcting and evaluating the necessity for increasing the dose of a medicine, as well as checking on the efficiency of the therapeutic line. The iodine-123 can also be used to mark other molecules such as in the use for the examination of the neural or cerebral flux and in the studies of neuro receptors.

A vital factor
In cardiology there are various uses for iodine-123, which help the doctor to understand the problem of the patient. “For example, if he had a heart attack, the examination taken with marked methyliodobenzylguanidine can confirm the area of arrhythmia. In the case of heart transplants, many times it is necessary to choose the receptor of a heart on the waiting list. There is a moment in which all of the factors involved, from the clinical or functional point of view, are similar, but the person with the lower concentration of noradrenalin in the myocardium is the most serious case and should, in statistical terms, die first if there is no solution. The examination with the labeled molecule of iodine-123 can identify who these people are on the waiting list for a heart transplant.

Meneghetti pointed even more to the case of people with occasional arrhythmias, caused by errors in the distribution of the neural network of myocardium and which could have their case more closely studied. The use of iodine-123 in the diagnosis of the thyroid gland will be smaller than the one with iodine-131, because it has a longer half-life of eight days. “This makes its availability much easier for the day-to-day necessities of the clinic”, explains the chemist Jair Mengatti, coordinator of production of the radioactive isotopes of Ipen. “However, even if the iodine -131 continues with a significant role in the diagnosis of the thyroid gland, the iodine-123 is unquestionably better in the marking of molecules for other types of examinations, for the excellence of the images which it produces and for the low radioactivity administered to the patient.”

Without impurities
The iodine-123 was previously produced by Ipen through the oxide of tellurium, but this substance contained a contaminant iodine-124. Incor worked in the past, in an academic form, with this iodine. If administered to a patient, even in small doses, the iodine-124 remains in the organism. Nonetheless, this impure iodine was used in sporadic cases, according to  Meneghetti: “Only when the benefit of its application compensated the risk from radiation by the 124, in the case of patients waiting for a new heart and with a short life expectancy should the transplant not happen.” With the xexon-124 gas, the iodine-123 guarantees, as well as the high quality of the image, the absence of impurities such as iodine 124.

In fact, close to 1.5 million people are being benefited by the radioactive isotopes produced by Ipen. Mengatti informs that the use of these products in Brazil has been growing at around 13% per year. Some, such as iodine-131 and iodine-123 have shown rises of 15%. “However, even with the speed of the growth, we are using the quantity of radioactive isotopes close to that of the Argentine.” Considering that Argentina has 1/4 of the population of Brazil, the Brazilian consumption needs to grow 300% to equal that of the Argentines.

Meneghetti, for his part, commented that the growth of nuclear medicine has been considerable: “We were at a very low level of application. The situation changed when the Brazilian Society of Nuclear Medicine began to pass out information amongst doctors on the benefits of nuclear examinations.” With the production of iodine-123 in São Paulo, a new advance in this area of medicine has been achieved.

The project
The development and the Implementation of the Method of Obtaining Iodine-123 by Way of the Irradiation of Xenon-124 at Ipen/Cnen/SP (nº 98/14218-6); Type Assistance to research program; Coordinator
Dr. Valdir Sciani – Institute of Energy and Nuclear Research (Ipen); Investment R$ 109,500.00 and US$ 50,000.00