Evaluation of 11C-PK11195 metabolites in venous blood of people with Down Syndrome

• Grant number: 21/02272-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2021
• End date: April 30, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Radiology
• Agreement: Instituto Jô Clemente
• Principal Investigator: Daniele de Paula Faria
• Grantee: Gabrielle dos Santos Carvalho
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/15167-1 - Translational neuroimaging in intellectual disability: evaluation of molecular changes associated with aging in Down Syndrome, AP.JP

Abstract

People with Down syndrome (DS) have chromosome 21 trisomy. This trisomy is considered to be the main reason for the high rate of onset of Alzheimer's disease in people with DS, and processes such as neuroinflammation and beta-amyloid plaque deposition are processes that happen during aging. It is possible to evaluate neuroinflammation by molecular imaging in vivo, using the positron emission tomography (PET) technique, using specific radiopharmaceuticals, such as 11C-PK11195. 11C-PK11195 binds to the 18 kDa translocator protein (TSPO), which is overexpressed in glial cells in the event of inflammation, and is then detected by PET equipment. The quantification of PET images can be done in a visual, semi-quantitative and / or quantitative way, and for quantitative analysis it is necessary to have information on the plasma quantity of the radiopharmaceutical, as well as its radioactive metabolites. The most reliable way to quantify radioactive metabolites is the analysis of arterial blood by HPLC (High Performance Liquid Chromatography) coupled to a radiation detector. In this project, the venous blood of people with Down Syndrome will be evaluated by HPLC to quantify radioactive metabolites, and these data will be compared with data from arterial blood from healthy people and with multiple sclerosis (data already existing in our laboratory). The purpose of this comparison is to standardize the analysis of venous blood, which is obtained in a less invasive way, to determine radioactive metabolites of 11C-PK11195, in order to make this analysis more viable in the population with Down syndrome. (AU)