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Clinical Analysis

Without marks on the antibody

Equipment carried out the diagnosis of breast and prostrate cancers and of leishmaniasis based on antigens

A new piece of equipment for diagnosing breast and prostrate cancers, and also capable of detecting leishmaniasis, an infectious disease that hits many poor areas of the country, is being concluded by a research group from the Molecular Nanotechnology Network of Interfaces (Renami), under the coordination of Oscar Malta, from the Federal University of Pernambuco (UFPE). The use of the prototype experimentally has already demonstrated that it is cheaper than other similar and imported test equipment. It has been given the name of Fluorim 1.0 and is based on the optical properties of a compound developed by the researchers that cannot have its secret unveiled yet, while it is not patented here in Brazil and abroad. A patent request for the substance should shortly be filed at the National Intellectual Property Institute (INPI).

According to the researchers, it is possible to say that it works as an optical marker for the illness and is synthesized starting from europium oxide. “Among the lanthanides, which in the Periodic Table are found in the Rare Earth Metals, europium is the most luminescent”, justifies professor Malta, who works at the Fundamental Chemistry Department of  UFPE and is the national coordinator of the Renami, a network set up by the Ministry of Science and Technology that brings together sixty researchers from seventeen  institutions throughout the country. “This oxide is a white powder obtained from a europium compound extracted from monazite sand (found on some beaches), where the major reserves of this chemical element are concentrated”, completes Malta.

The compound developed by the researchers is slightly different in its structure for detecting each one of the three diseases. It is made up into kits and has nanometric dimensions (in which 1 millimeter is divided into 1 million parts). Its function is to bind itself to the antigen produced by the disease being diagnosed. An antigen is the substance, normally a protein, produced by a virus or a bacterium, for example. In the human body, each antigen gains a specific antibody produced by the immunological system to combat each disease. They get together like a key fitting into a lock. When a drop of blood or a piece of cellular tissue of a patient is placed in the kit, the antigen linked to the antibody fixes onto the compound created by the researchers. Afterwards, within the equipment the sample received a beam of ultraviolet light of a specific wavelength.

The result is identified in the luminous signal reflected by the compound. Besides the presence of the disease, the examination also gives details about the degree of the patient’s infection. “In the case of the analysis of tissue originating from a biopsy (immobilized within a microscope slide), the idea is to map out all of its surface area and afterwards to reconstruct it by way of a graph that should represent the different degrees of infection”, says Jaílson Vieira de Melo, from the Chemistry Department of the Federal University of Rio Grande do Norte (UFRN), who also participated in the project.

To gauge the advance of the illness is one of the important advantages of this equipment. “The more advanced the illness is, the more intense will be the light emitted”, explains Malta. By this method, the researchers avoid any direct marking of the antibody, as in other types of similar exams, which can lead the device into errors. This happens because the organism frequently produces antibodies. By identifying the antigen and its quantity, the researchers can be certain about the illness. The method used is a type of fluoro-immune test, which serves for the analysis of a series of illnesses such as various types of cancer and syphilis. The problem is that the equipment that makes use of this method is imported and expensive. “We’re building an apparatus with the same principles, but with adaptations both in relation to the way of measuring that will be carried out on the tissue, and the kit, which is being used, and mainly in relation to costs”, says professor Melo. “This is a piece of apparatus based on those already in existence and adapted for the illnesses that we wish to diagnose, above all an unprecedented test for leishmaniasis.”

The prototype has the dimensions of a half meter squared box and cost R$ 30,000.00  – around 10% of the price of similar fluoro-immune test devices imported by blood banks centers, clinical analysis laboratories and hospitals in the country. The equipment is the result of a year and a half of research at the Renami, one of the four national research networks that are dedicated to the study of materials on a nanometric scale. Linked to the Renami Project, as well as UFPE and UFRN, are the Chemistry Institute of the University of Sao Paulo (USP), in the Paulista capital city, and USP’s Chemistry Department in the town of Ribeirão Preto. The testing phase will as yet involve a unit at the Oswaldo Cruz (Fiocruz) Foundation of  Recife, called the Aggeu Magalhães Research Center (CPqAM).

Definite diagnosis
One of the illnesses to be diagnosed by the new device is the American tegumentary leishmaniasis, with 1.5 million new cases per year in the world. In  Brazil, according to data from the National Health Foundation (Funasa), annually 35,000 new cases are notified. The researcher from Fiocruz in Recife, Luíza de Campos Reis, explained that the health professionals confront difficulties when attempting to diagnose the illness, also known as cutaneous leishmaniasis: “Currently a standard test for the diagnosis of leishmaniasis doesn’t exist, and very often only a combination diagnostic techniques offer exact and precise results”. The doctor has to bring together clinical, epidemiological and laboratory aspects. Luíza hopes that the new device will be an efficient means for identifying the disease.

Leishmaniasis is transmitted through the bite of the female blood sucking mosquito called phlebotomus, found in rural areas. The protozoa that causes the illness, the leishmania, lodges in man and other mammals, bringing about lesions in the mucus and cartilage. In the case of breast cancer, which in Brazil is the disease that causes most deaths in women, according to the National Cancer Institute (Inca), it is proposed to make use of the device for early diagnosis of the illness, after having made the discovery of some anomaly in breast testing examinations. The earlier it is identified, the greater are the chances of a cure. In Brazil around 10,000 deaths are registered annually to breast cancer. More than half of them occur to women between the ages of 40 and 69 years of age.

The use of Fluorim 1.0 for the diagnosis of prostate cancer, according to the Inca, for men, the second cause of deaths by this type of illness, will lower the cost of examinations. The device will analyze in cellular tissue from a biopsy the levels of prostate-specific antigen (acronym PSA). The Fluorim will identify only whether or not the patient has PSA. “We’re going to carry out the PSA because it is a relatively easy exam. And, it’s also a way of quickly testing the prototype”, explains professor Malta. When the calibration phase has been concluded, the team intends to validate the equipment at the National Sanitary Vigilance Agency (Anvisa) and at the National Metrology, Normalization and Industrial Quality Institute (Inmetro). The researchers’ expectation is that the device will reduce the cost of an examination for the diagnosis of prostate cancer by up to 30%. The test should be much cheaper than that currently carried out, whose cost runs at about R$ 70.00.

Once the test and validation stages have been completed, which should take a year, the team will move towards the commercialization of the product. This phase, the final and longest in a project of this type, is considered the most difficult by the physicist Cylon Gonçalves da Silva, the secretary of the Research and Development Programs Policy of the Ministry of Science and Technology (MCT). “From the laboratory bench to the industrial production line, to the store shelves and the consulting rooms and laboratories, this equipment will cover a lot of ground”, he advised. “This is a slow process and will cost a lot more than developing a prototype.”

The project, nevertheless, already has two positive signals that could shorten this journey. One comes from the MCT itself. “As the desire of the Ministry of Health is to fund the research and development of medical-dental and laboratory equipment, obviously a project such as this appears to be a natural candidate for support”, advances Gonçalves da Silva. The other comes from the Superintendence of the Tax Free Zone of Manaus (Suframa). Professor Oscar Malta hastened to add that he has already had contact with directors of the State run company. “They’ve signaled to me the possibility of producing the Fluorim 1.0 in a Suframa incubator company.”