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

• Grant number: 18/18112-3
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Duration: November 01, 2019 - October 31, 2021
• Field of knowledge: Engineering - Nuclear Engineering - Applications of Radioisotopes
• Convênio/Acordo: FINEP - PIPE/PAPPE Grant
• Principal Investigator: Sofia Nascimento dos Santos
• Grantee: Sofia Nascimento dos Santos
• Host Company: Sofia Nascimento dos Santos
• CNAE: Comércio atacadista de instrumentos e materiais para uso médico, cirúrgico, ortopédico e odontológico
• City: São Paulo
• Associated researchers: Alexander Henning Ulrich ; Emerson Soares Bernardes
• Associated research grant: 16/21870-1 - Validation of the use of a DNA aptamer specific for HER2 as a radiopharmaceutical for tumor imaging, AP.PIPE
• Associated scholarship(s): 21/00852-3 - Validation of the use of a specific DNA aptamer for HER2 as a radiopharmaceutical for tumor imaging, BP.TT; 21/01761-1 - Validation of the use of a DNA aptamer specific for HER2 as a radiopharmaceutical for tumor imaging, BP.TT; 20/00182-5 - Validation of the use of a DNA aptamer specific for HER2 as a radiopharmaceutical for tumor imaging, BP.TT; 19/23567-2 - Validation of the use of a DNA aptamer specific for HER2 as a radiopharmaceutical for tumor imaging, BP.TT; 19/23539-9 - Validation of the use of a HER2-specific DNA aptamer as a tumor imaging radiopharmaceutical, BP.PIPE

Abstract

Over 1.7 million women are diagnosed with breast cancer each year in the world. This type of cancer is divided into three subtypes (PR/ER positive, HER2 positive and triple negative). HER2-positive (25%) breast cancers over-express the ErbB-2 / HER2 human epidermal growth factor receptor 2. This type of cancer is one of the most aggressive with high metastatic potential. However, there are specific treatments for HER2-positive cancer, such as Trastuzumab. Despite the already use of Trastuzumab for the treatment of localized breast tumors, SUS recently launched a treatment (January 2018) for HER2 positive metastatic breast cancer (Diagnostic and Therapeutic Guidelines, Joint Ordinance No. 4), of 01/23/18). Thus, diagnostic methods capable of accurately identifying the presence of the HER2 receptor in tumors are increasingly required to assist in the prescription of the best therapy for the patient.The current method for the detection of HER2 in tumors is a biopsy. However, on average, 10-15% of biopsies in tumors are inconclusive or can not be performed. In the case of metastases, because they are scattered throughout the body and sometimes in inaccessible places, they often invalidate the definition of the breast tumor subtype. In these cases, the doctor only can prescribe the most aggressive standard treatment which, in addition, brings in the extreme side-effects.The detection of the number and location of metastases is nowadays performed by an imaging method SPECT or PET associated with Computed Tomography (SPECT / PET / CT ). The most commonly used radiopharmaceutical for this purpose is [18F] -fluorodeoxyglucose ([18F] FDG). In breast cancer, this PET / CT scan with [18F] FDG is done in patients with local neoplasm and patients with suspected distant disease (metastases in other organs). However, this radiopharmaceutical, has shown little specificity in the diagnosis of certain tumors because of its high uptake in inflammatory sites and healthy organs (mainly in the brain). Moreover, imaging with [18F] FDG does not allow to distinguish the subtype of tumor that the patient has nor the most appropriate therapy for this type of cancer.Thus, interest in alternative imaging agents with specific binding capacity to receptors, antigens, and enzymes has gained increasing interest in the medical community.In this project, through the use of molecular imaging agents with radionuclide, we intend to continue the development of a specific radiopharmaceutical against HER2 receptor for the diagnosis by SPECT / CT of HER2 positive tumors / metastases. This radiopharmaceutical, called HERtarget, will be marketed in the form of a "cold" kit (non-radioactive product), which can be radiolabeled in the clinics for use in patient. The use of this radiopharmaceutical will not only predict the level of progression of the disease but also help in planning the treatment and monitoring the response to therapy. Furthermore, our interest is concentrated in an area where there is already a clinical demand for new molecular imaging agents, in particular against HER2, which should allow for the successful commercialization of radiopharmaceuticals in the short term. (AU)