TY - JOUR T1 - [<sup>18</sup>F]FAZIN3: A novel PET imaging agent for Parkinson’s Disease JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 148 LP - 148 VL - 61 IS - supplement 1 AU - Phuc Lam AU - Stephanie Martinez AU - Krystal Patel AU - Christopher Liang AU - Jogeshwar Mukherjee Y1 - 2020/05/01 UR - http://jnm.snmjournals.org/content/61/supplement_1/148.abstract N2 - 148Objectives: Parkinsonian disorders may be either synucleinopathies or taupathies based on neuropathological characteristics. In an effort to develop PET imaging agents for synucleinopathies, we have carried out design of molecules that contain either Aβ-amyloid, dopamine receptor or Tau binding structures, since these may be overlapping features or interactions between α-synuclein aggregates in Parkinson’s disease (PD). Here we report results on a novel fluoroalkylated azaindole ([18F]FAZIN3) as a potential PET imaging agent for PD. Human post-mortem brain autoradiographic studies of [18F]FAZIN3 were carried out in cognitively normal (CN) controls, PD, and Alzheimer’s disease brains containing anterior cingulate (AC) and corpus callosum (CC). Methods: Human post-mortem brain tissues consisting of anterior cingulate and corpus callosum (controls (CN), n=6; age 81-90 total Tangle=1 to 3.5; PD, n=6, age 77-89, total Tangle= 2 to 7; AD, n=6, age 77-89, total Tangle = 10 to 15) were obtained from Banner Health, Sun City, Arizona. Brain slices (10 μm thick) consisting of both AC and CC of each subject were obtained by a Leica 1850 cryotome. Shown in Fig 1A and 1C are the brain slices of CN and PD, respectively. [18F]FAZIN3 was prepared using AZIN3-Tosyl and nucleophilic [18F] fluoride. Adjacent brain slices were incubated [18F]FAZIN3 (1 μCi/cc) in PBS (pH 7.4) buffer at 25 oC for 60 minutes. Using the Optiquant program (Packard Instruments Co), regions of interest were drawn and digital light units/ mm2 (DLU/mm2) were used to quantify the percentage binding of [18F]FAZIN3. Shown in Fig 1B and 1D are the brain slices of CN and PD, respectively, after exposure to [18F]FAZIN3. Results: All CN subjects exhibited lower [18F]FAZIN3 binding in the AC compared to the PD subjects. In the CN subjects, AC binding marginally increased with increasing total tangle score (R2= 0.6032). The gray matter and white matter were clearly delineated in the autoradiographic images as seen in Fig 1B and 1D. In the case of the PD subjects, AC exhibited a more than 2-fold increase in binding of [18F]FAZIN3 (PD/CN = 2.12) for AC. Unlike the CN subjects, the PD subjects showed poor correlation of total tangle versus [18F]FAZIN3 binding. Interestingly, in the AD subjects, even with a high total tangle score (10 to 15), [18F]FAZIN3 binding was lower in the AC than observed in PD (AD/CN = 2.04). The total averages of [18F]FAZIN3 binding of gray matter across CN, PD, and AD are shown in Figure 1E. Conclusions: The exquisite binding of [18F]FAZIN3 in the PD and AD brain samples suggests that it may be binding to unique Tau configurations. Further studies are underway to delineate the binding properties of [18F]FAZIN3 in taupathies such as progressive supranuclear palsy and corticobasal syndrome. Additional studies are planned to investigate the potential role of α-synuclein aggregates in the binding of [18F]FAZIN3. ER -