Descripción del proyecto
PET del encéfalo para el diagnóstico de enfermedades neurodegenerativas
Las enfermedades neurodegenerativas como el mal de Alzheimer y la enfermedad de Parkinson se han convertido en un problema médico significativo debido al envejecimiento de la población. En la actualidad, no existe una cura y el diagnóstico suele retrasarse debido a la falta de unas pruebas de diagnóstico adecuadas. El proyecto COLIBRI, financiado con fondos europeos, desarrollará un método de tomografía por emisión de positrones (PET, por sus siglas en inglés) basado en la química clic «in vivo» en el encéfalo. La absorción y la eliminación de compuestos específicos se optimizarán y probarán en modelos animales. El enfoque de toma de imágenes de COLIBRI PET tiene el potencial de aplicarse para el diagnóstico temprano de la neurodegeneración, así como para su seguimiento en pacientes que reciben varias intervenciones terapéuticas.
Objetivo
As the world’s population is living longer, age-related neurodegenerative diseases (ND) such as Alzheimer’s and Parkinson’s are becoming a larger global issue. To date, no cure exists, and the European Union considers the understanding and the diagnosis of ND as key research areas. In this context, the overall aim of the fellowship is the development of a versatile method for immuno based brain PET, as a general translational molecular research method that can also be applied for early diagnosis of ND and follow up of the efficacy of novel ND therapies. This will be realized through a pretargeting approach using in vivo click chemistry in brain. More specifically, I will investigate the usefulness of 18F-TCO (trans-cyclooctene derivatives) for pretargeted PET imaging of α-synuclein for Parkinson’s disease. The project will be divided into 4 objectives: (1) Design and synthesis of fluorine-18 labelled TCO derivatives with optimal brain uptake and clearance (“18F-brainTCO”), (2) Evaluation of in vivo kinetics of a polar peripheral blocking TCO derivative, (3) Tetrazine derivatization of an antibody (TzAb) targeting α-synuclein, investigation of in vitro and in vivo binding to α-synuclein, and in vitro and in vivo availability for click reaction, (4) In vitro (autoradiography) and in vivo (microPET/MR) imaging of the TzAb binding to α-synuclein using 18F-brainTCO. The success of COLIBRI will rest on its interdisciplinary since various scientific fields will be covered: organic synthesis, flow chemistry, antibody derivatization, radiochemistry, in vitro/ex vivo tests, in vivo tests in animal models and PET imaging. The project also includes work packages dedicated to the project management (personal career development plan, progress monitoring, budget, ethics and risk management), training (techniques, courses, supervision of students), and dissemination and communication (publications, reports, lab meetings, conferences, popularization events, Internet presence, ...).
Ámbito científico
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- natural sciencescomputer and information sciencesinternet
- medical and health sciencesclinical medicineradiologynuclear medicine
- natural scienceschemical sciencesnuclear chemistryradiochemistry
- medical and health sciencesbasic medicineneurologyparkinson
Programa(s)
Régimen de financiación
MSCA-IF-EF-RI - RI – Reintegration panelCoordinador
3000 Leuven
Bélgica