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Validation of the use of a DNA aptamer specific for HER2 as a radiopharmaceutical for tumor imaging

Grant number: 16/21870-1
Support type:Research Grants - Innovative Research in Small Business - PIPE
Duration: March 01, 2018 - November 30, 2018
Field of knowledge:Engineering - Nuclear Engineering - Applications of Radioisotopes
Principal Investigator:Sofia Nascimento dos Santos
Grantee:Sofia Nascimento dos Santos
Company:Sofia Nascimento dos Santos
City: São Paulo
Assoc. researchers: Arian Pérez Nario ; Fábio Fernando Alves da Silva ; Maria Renata Valente Brandão Freire ; Martha Sahylí Ortega Pijeira
Associated grant(s):18/18112-3 - Validation of the use of a DNA aptamer specific for HER2 as a radiopharmaceutical for tumor imaging, AP.PIPE
Associated scholarship(s):18/01662-0 - Validation of the use of a DNA aptamer specific for HER2 as a radiopharmaceutical for tumor imaging, BP.PIPE

Abstract

The non-invasive diagnosis and measurement of cellular and molecular processes in cancer patients by PET imaging associated with computed tomography (PET/CT), has considerably improved cancer therapy. So far, over 90% of the clinical trials aimed to detect tumors use the [18F] -fluorodeoxiglicose ([18F] FDG). However, this radiopharmaceutical has demonstrated poor specificity in the diagnosis of some tumors and has a high uptake in inflammatory sites and healthy organs. Therefore, the search for new alternative imaging agents, like receptors, antigens and enzymes with specific binding abilities, has gained increasing interest within the scientific community. Because of its high specificity, monoclonal antibodies and their fragments have been the radiopharmaceuticals of choice to target cancer cells. However, despite of its great success, antibodies are becoming gradually obsolete in imaging due to its longer half-life high in the bloodstream, hematologic toxicity and their low tissue penetration. In contrast to protein antibodies, aptamers offer unique chemical and biological characteristics based on their oligonucleotide properties, and have emerged as a potential new class of molecules for the diagnosis of tumors in vivo. This project, to be developed in partnership with the company Apttacore, proposes to validate the use of a specific DNA aptamer with high affinity for the cancer biomarker HER2 (highly expressed in breast, ovarian, head and neck and prostate cancers), for the diagnosis and imaging by PET/CT of tumors. To accomplish this, we intend to radiolabel this aptamer with 68Ga, and evaluate its specific binding to HER2 negative and positive tumor cells in vitro and in vivo. In addition, stability tests will be carried out in saline and serum. We expect to demonstrate this aptamer of DNA can identify with high specificity tumor cells expressing HER2 and have all the characteristics to be used in preclinical studies for the detection of tumors in vivo. Furthermore, our interest is focused on a research area (molecular imaging diagnostic) in which the use of antibodies is considered a disadvantage. Therefore, the clinical demand for new molecular imaging agents will allow a successful commercialization of aptamers in a short period of time. (AU)