Synthesis and radiolabeling with Ga-68 of peptides modified with novel bis(semicarbazone)-type metal-chelating systems. Influence of their chemical and biological properties on tumor processes.

• Grant number: 25/12735-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2025
• End date: July 31, 2027
• Field of knowledge: Engineering - Nuclear Engineering - Applications of Radioisotopes
• Principal Investigator: Luciana Malavolta Quaglio
• Grantee: Aline Morais de Souza
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/10265-8 - Cancer Theranostics Innovation Center (CancerThera), AP.CEPID

Abstract

Cancer is one of the most common causes of death in the world, second only to cardiovascular diseases. In the last ten years, there has been a 20% increase in the incidence of cancers, and it is estimated that by 2030, more than 25 million new cases will occur. In this sense, in an attempt to overcome the difficulties of classic treatments, such as the recurrence of neoplasia, new treatment perspectives are gaining ground, among them, molecular target therapies, with emphasis on peptides. The use of peptides has been growing in recent decades due to their intrinsic anti-tumorigenic action, which can lead to the inhibition of angiogenesis, the cell cycle, transcription, and signaling pathways of tumors, as well as the ability to act as a targeting molecule, due to the affinity for receptors overexpressed in neoplasias. The studies proposed in this project appear to us to be extremely relevant, as the use of potential peptide inhibitors GRGDYV and EEEEYFELV, which have high affinity for the integrin adhesion molecule alfavbeta3 and the EGF receptor, respectively, both of which are overexpressed in different neoplasms, can inhibit the tumor growth process. As a targeting biomolecule, these peptides can be used as a vehicle to carry, for example, a radionuclide aiding in diagnosis and/or treatment, as an antitumor agent, depending on the type of radiation emitted by the radionuclide attached to it. Thus, the present project aims to obtain modified GRGDYV and EEEEYFELV peptide fragments incorporating two spacers and two different chelating agents for the physicochemical evaluation of the synthesized complexes. These complexes will then be assessed for their interaction with the integrin alfavbeta3 adhesion molecule and the EGF receptor in both cell lines and a glioblastoma tumor model.