Binding of the Radioligand SIL23 to α-Synuclein Fibrils in Parkinson Disease Brain Tissue Establishes Feasibility and Screening Approaches for Developing a Parkinson Disease Imaging Agent

Bagchi, Devika P.; Yu, Lihai; Perlmutter, Joel S.; Xu, Jinbin; Mach, Robert H.; Tu, Zhude; Kotzbauer, Paul T.

doi:10.1371/journal.pone.0055031

Cited by 104 publications

(130 citation statements)

References 42 publications

(44 reference statements)

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“…Politis (2014) has listed over 100 possibly useful radioligands and more are in development (Appel et al, 2015; Bagchi et al, 2013; Boassa et al, 2013; Bu et al, 2014; Coakeley & Strafella, 2015; Kiessling, 2014). Many radioligands probe neurotransmitter systems and depend on sophisticated application of the biochemistry of neurotransmitters (Brooks, 2005; Brooks & Pavese, 2011; Hammoud et al, 2007).…”

Section: Neuroimaging Methodsmentioning

confidence: 99%

Neuroimaging of Parkinson's disease: Expanding views

Weingarten

Sundman

Hickey

et al. 2015

Neuroscience & Biobehavioral Reviews

137

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Advances in molecular and structural and functional neuroimaging are rapidly expanding the complexity of neurobiological understanding of Parkinson’s disease (PD). This review article begins with an introduction to PD neurobiology as a foundation for interpreting neuroimaging findings that may further lead to more integrated and comprehensive understanding of PD. Diverse areas of PD neuroimaging are then reviewed and summarized, including positron emission tomography, single photon emission computed tomography, magnetic resonance spectroscopy and imaging, transcranial sonography, magnetoencephalography, and multimodal imaging, with focus on human studies published over the last five years. These included studies on differential diagnosis, co-morbidity, genetic and prodromal PD, and treatments from L-DOPA to brain stimulation approaches, transplantation and gene therapies. Overall, neuroimaging has shown that PD is a neurodegenerative disorder involving many neurotransmitters, brain regions, structural and functional connections, and neurocognitive systems. A broad neurobiological understanding of PD will be essential for translational efforts to develop better treatments and preventive strategies. Many questions remain and we conclude with some suggestions for future directions of neuroimaging of PD.

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Section: Neuroimaging Methodsmentioning

confidence: 99%

Neuroimaging of Parkinson's disease: Expanding views

Weingarten

Sundman

Hickey

et al. 2015

Neuroscience & Biobehavioral Reviews

137

View full text Add to dashboard Cite

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“…Benzoxazole compounds that bind to β-amyloid might also bind to α synuclein and can be labelled with either 11 C (S24) or 18 F (S25), but are not selective and have not yet gained widespread acceptance for the study of Lewy body disorders. 123 I-SIL23 is a phenothiazine that binds to synuclein fibrils in vitro (and in vivo in mouse models), 43 but its affinity is relatively low, as is its specificity for synuclein compared with Aβ and tau. Several compounds with improved specificity for abnormally phosphorylated tau have been described.…”

Section: Abnormal Protein Depositionmentioning

confidence: 99%

Imaging insights into basal ganglia function, Parkinson's disease, and dystonia

Stoessl¹,

Lehericy²,

Strafella³

2014

The Lancet

141

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Recent advances in structural and functional imaging have greatly improved our ability to assess normal functions of the basal ganglia, diagnose parkinsonian syndromes, understand the pathophysiology of parkinsonism and other movement disorders, and detect and monitor disease progression. Radionuclide imaging is the best way to detect and monitor dopamine deficiency, and will probably continue to be the best biomarker for assessment of the effects of disease-modifying therapies. However, advances in magnetic resonance enable the separation of patients with Parkinson's disease from healthy controls, and show great promise for differentiation between Parkinson's disease and other akinetic-rigid syndromes. Radionuclide imaging is useful to show the dopaminergic basis for both motor and behavioural complications of Parkinson's disease and its treatment, and alterations in non-dopaminergic systems. Both PET and MRI can be used to study patterns of functional connectivity in the brain, which is disrupted in Parkinson's disease and in association with its complications, and in other basal-ganglia disorders such as dystonia, in which an anatomical substrate is not otherwise apparent. Functional imaging is increasingly used to assess underlying pathological processes such as neuroinflammation and abnormal protein Correspondence to: Prof A J Stoessl,

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“…Development of such a molecular imaging radiotracer has been the focus of much research but is not yet forthcoming. 1 …”

Section: Introductionmentioning

confidence: 99%

Neuroimaging biomarkers for Parkinson disease: Facts and fantasy

Perlmutter¹,

Norris

2014

Annals of Neurology

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In this grand rounds, we focus on development, validation, and application of neuroimaging biomarkers for Parkinson disease (PD). We cover whether such biomarkers can be used to identify presymptomatic individuals (probably yes), provide a measure of PD severity (in a limited fashion, but frequently done poorly), investigate pathophysiology of parkinsonian disorders (yes, if done carefully), play a role in differential diagnosis of parkinsonism (not well), and investigate pathology underlying cognitive impairment (yes, in conjunction with postmortem data). Along the way, we clarify several issues about definitions of biomarkers and surrogate endpoints. The goal of this lecture is to provide a basis for interpreting current literature and newly proposed clinical tools in PD. In the end, one should be able to critically distinguish fact from fantasy. Ann Neurol 2014;76:769–783

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Binding of the Radioligand SIL23 to α-Synuclein Fibrils in Parkinson Disease Brain Tissue Establishes Feasibility and Screening Approaches for Developing a Parkinson Disease Imaging Agent

Cited by 104 publications

References 42 publications

Neuroimaging of Parkinson's disease: Expanding views

Neuroimaging of Parkinson's disease: Expanding views

Imaging insights into basal ganglia function, Parkinson's disease, and dystonia

Neuroimaging biomarkers for Parkinson disease: Facts and fantasy

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