Aggregated alpha-synuclein is one of the primary components of Lewy bodies which are a hallmark feature in the brains of patients with neurodegenerative diseases such as Parkinson’s disease (PD). Currently, there are no imaging tools available to monitor α-synuclein in PD patients; a selective PET ligand would greatly help drug development efforts for PD in addition to the diagnosis and prognosis of α-synuclein associated diseases. The aim of this study was to evaluate [18F]IMA201 as a potential PET ligand for delineation of α-synuclein in patients with PD. Animal experiments were conducted in accordance with the UK Animals (Scientific Procedures) Act 1986 and human tissue was ethically sourced from the Parkinson’s UK Brain Bank. [18F]IMA201 was prepared following the recently developed copper II-mediated 18F-fluorination methodology.1 Anatomically adjacent fresh frozen tissue sections (10 μm) from the cortical region of three individual PD patients were cut and fixed in 4% paraformaldehyde. Sections were incubated with increasing concentrations of [18F]IMA201 (0.3, 1, 10 nM) for 45 minutes, washed twice and apposed to phosphor-imager plates. Specific binding (SB) was identified by homologous block (10 μM) and ligand binding was quantified using a standard curve. The presence of α-synuclein was confirmed with immunohistochemistry in anatomically adjacent slides. Dynamic PET scans were conducted under baseline conditions (2.5 % isoflurane) and following pre-treatment with unlabelled IMA201 (2 mg/kg i.v.) to determine in vivo regional brain uptake of [18F]IMA201 in a healthy male Sprague Dawley rat (n=1). IMA201 was successfully labelled with 18F with a radiochemical yield of 150-400MBq and mean specific activity of 10±11 GBq/µmol (n=3). [18F]IMA201 demonstrated a heterogenous SB signal in brain tissue of three patients at three different concentrations (0.3nM: 6.2, 22 and 6.5 DLU/mm2/Bq; 1nM: 0, 120 and 40 DLU/mm2/Bq; 10nM: 390, 370 and 100 DLU/mm2/Bq). Percentage SB ranged from 0 – 87%, which was consistent with the heterogenous expression of α-synuclein between patients as determined by immunohistochemistry. [18F]IMA201 demonstrated good brain penetration in a healthy male rat with reversible kinetics during the time of the scanning period. The successful labelling, SB characteristics and in vivo kinetic profile of [18F]IMA201 suggest that this is a potential candidate for monitoring α-synuclein in the CNS. Radiosynthesis optimisation to allow clinical translation and further studies investigating the selectivity of [18F]IMA201 for α-synuclein over other misfolded proteins in patient brains, including the evaluation of a SB signal in a rodent model of PD, are required to confirm the potential of [18F]IMA201 in clinical applications and neurodegenerative drug development.