[18F]Nifene PET/CT Imaging in Mice: Improved Methods and Preliminary Studies of α4β2* Nicotinic Acetylcholinergic Receptors in Transgenic A53T Mouse Model of α-Synucleinopathy and Post-Mortem Human Parkinson’s Disease

Abstract

We report [18F]nifene binding to α4β2* nicotinic acetylcholinergic receptors (nAChRs) in Parkinson’s disease (PD). The study used transgenic Hualpha-Syn(A53T) PD mouse model of α-synucleinopathy for PET/CT studies in vivo and autoradiography in vitro. Additionally, postmortem human PD brain sections comprising of anterior cingulate were used in vitro to assess translation to human studies. Because the small size of mice brain poses challenges for PET imaging, improved methods for radiosynthesis of [18F]nifene and simplified PET/CT procedures in mice were developed by comparing intravenous (IV) and intraperitoneal (IP) administered [18F]nifene. An optimal PET/CT imaging time of 30–60 min post injection of [18F]nifene was established to provide thalamus to cerebellum ratio of 2.5 (with IV) and 2 (with IP). Transgenic Hualpha-Syn(A53T) mice brain slices exhibited 20–35% decrease while in vivo a 20–30% decrease of [18F]nifene was observed. Lewy bodies and α-synuclein aggregates were confirmed in human PD brain sections which lowered the [18F]nifene binding by more than 50% in anterior cingulate. Thus [18F]nifene offers a valuable tool for PET imaging studies of PD.

[124I]IBETA: A New Aβ Plaque Positron Emission Tomography Imaging Agent for Alzheimer’s Disease

“…All in vivo images were analyzed using Inveon Research Workplace (IRW) software (Siemens Medical Solutions, Knoxville, TN, USA) and PMOD Software (PMOD Technologies, Zurich, Switzerland). Whole-body PET/CT images were analyzed using the IRW software for [ 124 I]IBETA uptake and any other CT anomalies in the whole-body images [ 24 ]. For additional brain quantitative analysis, brain images were also analyzed using PMOD, with PET images co-registered to a mouse brain MRI template [ 24 , 25 ].…”

“…Whole-body PET/CT images were analyzed using the IRW software for [ 124 I]IBETA uptake and any other CT anomalies in the whole-body images [ 24 ]. For additional brain quantitative analysis, brain images were also analyzed using PMOD, with PET images co-registered to a mouse brain MRI template [ 24 , 25 ]. The magnitude of [ 124 I]IBETA in each volume of interest, VOI (in kBq/mL), was measured.…”

Development of [124/125I]IAZA as a New Proteinopathy Imaging Agent for Alzheimer’s Disease

“…In anticipation of undertaking future in vivo studies for the evaluation of Aβ drugs [ 21 ] and testing using other proteinopathy animal models [ 22 , 23 , 24 ], [ 124 I]IAZA was successfully prepared. Excellent binding of [ 124 I]IAZA was observed in the AD brain temporal cortex as well as the AC.…”

Elevated Monoamine Oxidase-A in Anterior Cingulate of Post-Mortem Human Parkinson’s Disease: A Potential Surrogate Biomarker for Lewy Bodies?

“…Nevertheless, the presence of abundant mitochondria (normal and dysphoric) in LB provides a good surrogate biomarker for LB and thus for PD. Imaging probes have been used for PD that measure loss of metabolism and other protein targets along the neurotransmitter-receptor pathways and are thus “cold spot” imaging agents [ 39 , 40 , 41 , 42 ]. Increased [ 18 F]FAZIN3 binding in PD with the increased presence of LB is a novel “hot spot” imaging approach ( Figure 1 and Figure 2 ).…”