Study of new imaging agents in experimental atherosclerosis: mimotope peptides of electronegative LDL

• Grant number: 14/11135-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 31, 2014
• End date: June 06, 2015
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Dulcineia Saes Parra Abdalla
• Grantee: Soraya Megumi Kazuma
• Supervisor: Yongjian Liu
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Washington, United States
• Associated to the scholarship: 13/02353-8 - Experimental atherosclerosis studies using Positron Emission Tomography (PET-SCAN), BP.DR

Abstract

Atherosclerosis is a disease of large arteries which affects a great part of the world population. In the atherosclerotic lesions, several self-antigens can be found, including modified lipoproteins as the electronegative LDL [LDL(-)] that presents pro-inflammatory effects contributing with atherosclerosis progression. Our research group (Abdalla, DSP) has selected mimotope peptides of LDL(-) using the phage display technique. These peptides may mimic parts of LDL(-) and are recognized by two monoclonal antibodies which are highly specific for LDL(-). These mimotope peptides have 8 aminoacids in their sequence with 2 cysteines between their ends forming a disulfide bond which provides them a circular structure. Many peptides have been developed as imaging agents in positron emission tomography (PET), because they have high affinity to their target, a good biodistribution profile and a rapid clearance from the blood. There are many possibilities of radiolabeling peptides with radioisotopes which could be used in PET, including 18F, 64Cu and 68Ga. Considering that LDL(-) has an important role in atherosclerotic disease, the aim of this study is to investigate the use of the LDL(-) mimetic peptides as molecular imaging agents for detection of their possible targets into the atherosclerotic lesions in animal models using microPET equipment. (AU)