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Pre-clinical evaluation of a new radiotracer with diagnostic purposes in immuno-inflammatory diseases expressing Angiotensin II type 1 receptor

Abstract

Multiple sclerosis (EM) is a progressive, chronic, autoimmune, and incurable disease characterized by inflammation and demyelination in the central nervous system (SNC). It is one of the most common neurological disorders in the world and the main cause of non-traumatic neurological disability in young adults, especially women. The mean age for onset of the disease is 30 years, and approximately 50% of patients require permanent wheelchair use after 25 years of diagnosis. Recently, in Brazil through the ordinance No. 10 of April 2nd, 2018, of the Ministry of Health, the incorporation of teriflunomide, dimethyl fumarate and fingolimod for the treatment of EM was approved in the Unified Health System (SUS). However, EM treatments to improve the patient's quality of life are expensive and are only prescribed after a conclusive diagnosis of the disease. In addition, the response to existing treatments depends on the clinical course of the disease.The diagnosis of EM is based on a set of tests including neurological examination, magnetic resonance imaging (IRM), evoked potential testing, and lumbar puncture. However, due to the complexity of EM, in some cases these tests are insufficient to establish a conclusive and early diagnosis that allows the rapid prescription of medication.Molecular imaging through Positron Emission Tomography associated with Computed Tomography (PET/CT) and a noninvasive modality with growing applications in neurology, providing in vivo metabolic information, and morphological data. PET imaging uses radiotracer containing positron emitters, and, unlike MRI, allows the visualization and quantification of a specific target with high sensitivity. Thus, depending on the radiotracer used, with the PET technology it is possible to obtain an early diagnosis, to evaluate the progression of the disease and therapeutic effectiveness. Despite all the advantages of PET diagnosis, to date, there are no specific radiopharmaceuticals for multiple sclerosis of use in clinical routine.It has been widely demonstrated that angiotensin II type 1 receptor (AT1R) is involved in the inflammation and pathogenesis of multiple sclerosis. Losartan, an AT1R inhibitor, is a low-cost drug widely used to treat hypertension and cardiovascular diseases. Recently, our group developed a new AT1R radioligand for PET imaging via labeling of losartan with fluorine-18 (18F), with high binding affinity. Therefore, the aim of this project is the pre-clinical evaluation of 18F-losartan (novel molecule) as a specific radiotracer of the AT1R for the diagnose of multiple sclerosis through PET/CT imaging. We hope to demonstrate that 18F-losartan is a specific radiotracer for the diagnosis of multiple sclerosis through the PET imaging of the AT1R. In addition, because of the high detection sensitivity of PET imaging and the favorable 18F properties for image resolution, 18F-losartan (prepared in a simple and fast way) represents a radiotracer with high potential for commercialization in the national and international market in short time. (AU)

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VEICULO: TITULO (DATA)