## 1 Introduction  
Although Parkinson's disease (PD) is a degenerative neurological disorder characterized by motor symptoms, it is also known to be closely associated with dementia [1]. The primary neuropathologic change in PD, the degeneration of dopaminergic neurons, occurs in the substantia nigra, accompanied by Lewy bodies (LB) and Lewy neurites (LN). To date, the pathogenic mechanism of PD is not fully understood [2]. The diagnosis of PD is primarily based on the clinical symptoms, such as resting tremor, bradykinesia and rigidity. Because the current treatment for PD is to minimize the disease symptoms in the patients [1,3], a method of diagnosing PD at a very early stage would greatly help physicians to design the therapy accordingly. \(a\)-Synuclein (\(a\)-syn) is a presynaptic terminal protein that consists of 140 amino acids; the aggregation of \(a\)-syn is considered the pathological hallmark of PD. \(a\)-Syn plays an important role in the central nervous system (CNS) in synaptic vesicle recycling; it also regulates the synthesis, storage and release of neurotransmitters [4]. It is specifically upregulated in a discrete population of presynaptic terminals of the brain during acquisition-related synaptic rearrangement [5]. \(a\)-Syn naturally exists in a highly soluble, unfolded state [6,7]. However, in PD brains, insoluble aggregation of misfolded fibrillar \(a\)-syn occurs in LB and LN, which may cause synaptic dysfunction and neuronal cell death [8, 9, 10, 11]. Positron emission tomography (PET) is a non-invasive imaging modality that can provide the functional information of a living subject at the molecular and cellular level. Current diagnostic PET radioligands for PD target either the dopaminergic system (pre-synaptic and post-synaptic dopamine activity) or vesicular monoamine transporter type 2 (VMAT2) [12,13]. Unfortunately, such imaging strategies have difficulty in distinguishing PD from other parkinsonian syndromes that also result in the degeneration of nigrostriatal projections [14,15]. In addition, dopaminergic medications used for symptomatic treatment may alter striatal uptake of these agents, limiting their reliability for measuring disease progression [16]. In contrast, \(a\)-syn is a valuable imaging target for PD, because fibrillar \(a\)-syn deposition in LB and LN distinguishes PD from other disorders and is the defining feature for post-mortem pathologic diagnosis. Thus, a small molecular PET radiotracer with high affinity and selectivity to fibrillar \(a\)-syn protein could be used to quantify the level of \(a\)-syn aggregation non-invasively. This will not only improve the diagnostic accuracy of PD, but also provide a tool to improve the understanding of disease progression and monitor the therapeutic efficacy in clinical trials. Our group previously reported the syntheses of a class of tricyclic analogues and their _in vitro_ binding affinities towards \(a\)-syn fibrils; several lead compounds were identified with moderateaffinities for \(\alpha\)-syn fibrils (\(K_{i}<70\) nM) (Figure 1, **2a**, **2b**) [17]. Compounds **2a** and **2b** also displayed favorable binding selectivity to \(\alpha\)-synuclein aggregation compared to A\(\beta\) and tau protein: for **2a**, \(K_{i\text{-a-syn}}/K_{i\text{-A}\beta}>3\)-fold and \(K_{i\text{-a-syn}}/K_{i\text{-tau}}>4\)-fold; for **2b**, \(K_{i\text{-a-syn}}/K_{i\text{-A}\beta}=2.1\)-fold and \(K_{i\text{-a-syn}}/K_{i\text{-tau}}=2.5\)-fold [18]. The radioiodinated ligand, [\({}^{125}\)I]**1**, was synthesized to establish a methodology for screening the \(\alpha\)-syn fibril binding affinity of new ligands using a competition binding assay [18]. The affinities for **2a** and **2b** were determined using this [\({}^{125}\)I]**1** assay, and the resulting \(K_{i}\) values (66.2 nM for **2a**, 19.9 nM for **2b**) were in the same range as the values obtained by the Thioflavin T assay.