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 project was 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 efficacy of novel ND therapies. This is realized through a pretargeting approach using in vivo click chemistry in brain. More specifically, we investigated the usefulness of 18F-TCO (transcyclooctene derivatives) for pretargeted PET imaging of α-synuclein for Parkinson’s disease. The project was 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 project also included work packages dedicated to the project management, training, and dissemination and communication.