Dementia associated with PD (PDD) is common (affecting up to 80% of patients long-term) and highly disabling. Informative biomarkers are urgently needed to understand the pathology of PDD, to improve the early detection of cognitive deficits and to facilitate the development of treatments for PDD. Nuclear imaging technologies have the potential to produce such biomarkers. Numerous studies have used 11C-PIB to measure amyloid burden in Alzheimer's disease (AD) and other dementing illnesses. However, the experience with amyloid imaging in PD has been limited, in spite of post-mortem evidence for substantial amyloid deposition in patients with PD. One of the impediments to conducting additional studies with 11C-PIB has been the short half life of 11C (H20 min), necessitating an on-site cyclotron and in-house radiochemistry expertise. Since the PET isotope 18F has a 110 minute half life and a well established nationwide distribution network, it has been our long standing corporate goal to develop an 18F amyloid imaging agent for amyloid plaques. We have recently developed and validated in human trials such an agent, 18F-AV-45, which is easy to use, can be made cheaply and reliably, and can be distributed on a regional basis. Most importantly, the compound shows an excellent ability (as good as or better than 11C-PIB) to image amyloid plaques in Alzheimer's disease. In this STTR grant we propose to conduct the first ever clinical trial of 18F-AV-45 in PD patients. The over-arching aim of this study is to use 18F-AV-45 imaging of amyloid burden as a biomarker to test the relationship between amyloid burden and cognitive functioning in PD. We will image 25 PD subjects over 2 years with 18F-AV-45 and will compare imaging results with clinical data and CSF biomarkers (tau and a-beta) of amyloid pathology. We hypothesize that 18F-AV-45 binding will be associated with greater degrees of overall cognitive impairment, shorter interval between onset of motor and cognitive impairment, and pattern of CSF biomarkers reflecting amyloid pathology.
Public Health Relevance: Successful validation of amyloid imaging as a biomarker for cognitive impairment in Parkinson's disease (PD) would represent a significant milestone in improving the diagnosis and treatment of this highly disabling feature of PD, and would represent a significant commercial opportunity for molecular imaging of these patients. However, little information is currently available regarding the amyloid burden, as measured by molecular imaging, in patients with PD or dementia associated with PD (PDD). 18F-AV- 45 is a fluorinated PET isotope that has favorable properties and has been shown to accurately identify amyloid pathology in Alzheimer's patients. In this project, we propose to use 18F-AV-45 to image amyloid pathology in patients with PD with cognitive impairment for the first time. Avid Radiopharmaceuticals is an experienced leader in developing new commercial PET tracers and is collaborating with world-experts on cognitive impairment in PD to conduct this clinical trial of amyloid imaging in PD and PDD.
Thesaurus Terms: Affect; Age; Alzheimer; Alzheimer Beta-Protein; Alzheimer Disease; Alzheimer Sclerosis; Alzheimer Syndrome; Alzheimer's; Alzheimer's Disease; Alzheimer's Amyloid; Alzheimers Dementia; Alzheimers Disease; Amentia; Amyloid; Amyloid Alzeheimer's Dementia Amyloid Protein; Amyloid Beta-Peptide; Amyloid Fibril Protein (Alzheimer's); Amyloid Plaques; Amyloid Protein A4; Amyloid Substance; Amyloid Beta-Protein; Amyloid Beta-Protein, Alzheimer's; Amyloid Deposition; Analysis, Data; Atrophic; Atrophy; Binding; Binding (Molecular Function); Biochemical Markers; Brain; Care Giver Burden; Caregiver Burden; Cell/Tissue, Immunohistochemistry; Clinical; Clinical Data; Clinical Trials; Clinical Trials, Unspecified; Cognitive; Cognitive Disturbance; Cognitive Impairment; Cognitive Manifestations; Cognitive Symptoms; Cognitive Decline; Cognitive Deficits; Cognitive Function Abnormal; Complication; Conduct Clinical Trials; Cyclotrons; Data Analyses; Dementia; Dementia With Lewy Bodies; Dementia, Alzheimer Type; Dementia, Lewy Body; Dementia, Primary Senile Degenerative; Dementia, Senile; Diagnosis; Diffuse Lewy Body Disease; Disease; Disorder; Disturbance In Cognition; Early Diagnosis; Emergent Technologies; Emerging Technologies; Encephalon; Encephalons; Goals; Grant; Half-Life; Half-Lifes; Housing; Human; Human, General; Ihc; Idiopathic Parkinson Disease; Image; Imaging Technology; Immunohistochemistry; Immunohistochemistry Staining Method; Impaired Cognition; Isotopes; Knowledge; Label; Lewy Bodies; Lewy Body Disease; Lewy Body Disease, Cortical; Lewy Body Parkinson Disease; Lewy Body Type Senile Dementia; Mr Imaging; Mr Tomography; Mri; Mt-Bound Tau; Magnetic Resonance Imaging; Magnetic Resonance Imaging Scan; Man (Taxonomy); Man, Modern; Markers, Biochemical; Measures; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; Medical Imaging, Positron Emission Tomography; Memory Deficit; Memory Impairment; Molecular Interaction; Mortality; Mortality Vital Statistics; Motor; Nmr Imaging; Nmr Tomography; Nervous System, Brain; Neuritic Plaques; Neurobehavioral Manifestations; Nuclear; Nuclear Magnetic Resonance Imaging; Pet; Pet Scan; Pet Imaging; Petscan; Pett; Paralysis Agitans; Parkinson; Parkinson Disease; Parkinson's; Parkinson's Disease; Parkinsons Disease; Pathology; Patient Participation; Patients; Pattern; Performance; Pittsburgh Compound-B; Positron Emission Tomography Scan; Positron-Emission Tomography; Primary Parkinsonism; Primary Senile Degenerative Dementia; Property; Property, Loinc Axis 2; Proton Magnetic Resonance Spectroscopic Imaging; Rad.-Pet; Radiation Chemistry; Radiochemistry; Radiopharmaceutical Compound; Radiopharmaceuticals; Research; Research Specimen; Risk Factors; Role; Sttr; Senile Plaques; Signs And Symptoms, Neurobehavioral; Site; Small Business Technology Transfer Research; Specimen; Tag; Temporal Lobe; Testing; Therapeutic; Time; Tracer; Validation; Zeugmatography; A Beta Peptide; Abeta; Amyloid Beta; Amyloid Beta Plaque; Amyloid Imaging; Amyloid Pathology; Amyloid-B Plaque; Amyloid-B Protein; Base; Beta Amyloid Associated Pathology; Beta Amyloid Fibril; Beta Amyloid Pathology; Biomarker; Care Giver Stress; Caregiver Stress; Clinical Investigation; Cognitive Dysfunction; Cognitive Function; Cognitive Loss; Cognitively Impaired; Cored Plaque; Dementia Of The Alzheimer Type; Diffuse Plaque; Disability; Disease/Disorder; Early Detection; Experience; Imaging; Improved; Intervention Development; Ligand Pib; Meetings; Microtubule Associated Protein Tau; Microtubule Bound Tau; Microtubule-Associated Protein Tau; Microtubule-Bound Tau; Mild Cognitive Disorder; Mild Cognitive Impairment; Mild Neurocognitive Disorder; Molecular Imaging; Primary Degenerative Dementia; Public Health Relevance; Radioactive Drugs; Senile Dementia Of The Alzheimer Type; Social Role; Soluble Amyloid Precursor Protein; Tau; Tau Proteins; Tau Factor; Temporal Cortex; Temporal Lobe/Cortex; Therapy Development; Treatment Development
