Molecular Imaging of Proteinopathy in Neurodegenerative Disease (Nasrallah)
Alzheimer’s disease is the most common neurodegenerative cause of dementia and is characterized by the accumulation of amyloid plaques and tau protein-containing neurofibrillary tangles. Both of these protein deposits (‘proteinopathies’) can be measured using PET imaging. The laboratory has collaborative studies investigating the relationships between amyloid and tau depositions and effects on brain structure, as measured by MR. We aim to leverage advanced image analytic methods, in collaboration with researchers at the Center for Biomedical Image Computing and Analytics at the University of Pennsylvania.
Nicotine Receptor Availability and Metabolism (Dubroff)
Smoking and nicotine addiction continue to represent the greatest cause of preventable morbidity and mortality in the United States as well as worldwide. Smokers who metabolize nicotine more slowly (measured by the nicotine metabolite ratio (NMR) of 3'-hydroxycotinine/cotinine) have a higher likelihood of successful smoking cessation using nicotine replacement therapy. Faster hepatic nicotine metabolism has been associated with elevated craving and withdrawal scores. Using 2-[18F]FA PET imaging, specific for the nicotinic acetylcholine receptor (nAChR) α4β2* subunit, we have demonstrated reduced thalamic nAChR availability in slow nicotine metabolizing smokers (NMR < 0.26) compared to other smokers following overnight abstinence. The goals of this study are (1) to determine how the duration of nicotine abstinence (24 vs 48 hours) affects nAChR availability in normal vs. slow nicotine metabolizers and (2) examine the effect of an intravenous nicotine challenge on nAChR availability in normal and slow nicotine metabolizers.
Neuroinflammation represents an emerging pathophysiological process recognized to contribute to a spectrum of neurological disease including Alzheimer’s disease, Parkinson’s disease, schizophrenia, nicotine dependence, alcohol use disorder, and cannabis use disorder.
in Parkinson’s Disease (Dubroff)
Nitric oxide (NO), the end product of the inducible form of NO synthase (iNOS), is an important mediator of a variety of inflammatory diseases. [18F]-6-(2-fluoro-propyl)-4-methylpyridin-2-amine (also called [18F]NOS), developmed by Dr. Robert Mach, is a positron emitting radiopharmaceutical which permits the visualization and measurement by PET imaging of in vivo iNOS expression as a marker of inflammation. [18F]NOS has been successfully used to image iNOS expression in humans to characterize oxidative stress and inflammation in transplanted heart and in pulmonary inflammation. The goal of this research study is to evaluate [18F]NOS as a surrogate biomarker of “neurotoxic”, termed M1-polarized, neuroinflammation in PD patients.
in Alzheimer’s Disease (Nasrallah)
PET imaging has been used to non-invasively measure neuroinflammation using a number of radiotracers that target the translocator protein (TSPO), also known as the peripheral benzodiazepine receptor (PBR), an 18 kDa protein found on the outer mitochondrial membrane throughout the brain and entire body. Changes in TSPO radiotracer binding as measured by PET imaging imply an immunogenic response via microglial activation. However, there are shortcomings using this strategy. The goal of this study is measure neuroinflammation in Alzheimer’s disease using two different PET imaging agents: (1) [11C]PBR28 that targets TSPO and (2) [18F]NOS that targets the inducible form of nitric oxide synthase (iNOS) known to be unregulated in acute and chronic inflammation.