EAAT2 PET Tracer for Dementia
Palo Alto (17 mi)Overseen byDavid Wilson, MD, PhD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: David Wilson
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial tests a new imaging agent that can be seen with a PET scan to detect early brain changes in patients with Alzheimer's disease and frontotemporal dementia. The agent targets a specific brain protein that is less active in these diseases. By identifying these changes early, doctors hope to improve diagnosis and treatment.
What data supports the idea that EAAT2 PET Tracer for Dementia is an effective treatment?The available research does not provide specific data on the effectiveness of EAAT2 PET Tracer for Dementia as a treatment. Instead, it discusses the use of PET imaging in diagnosing dementia and Alzheimer's disease, highlighting the role of different tracers in understanding brain changes and aiding in diagnosis. While PET imaging is valuable for early diagnosis and understanding dementia, there is no direct evidence in the provided information that EAAT2 PET Tracer is an effective treatment for dementia.2341011
Is the EAAT2 PET Tracer for Dementia a promising treatment?The EAAT2 PET Tracer for Dementia is a promising treatment because it helps doctors see important changes in the brain related to dementia. This can improve the diagnosis and understanding of the disease, potentially leading to better care for patients.567911
What safety data exists for the EAAT2 PET tracer for dementia?The provided research does not contain specific safety data for the EAAT2 PET tracer, also known as [18F]RP-115 or Fluorine-18 labeled RP115. The studies focus on other PET tracers like 18F-PI-2620, [18F] AV-45, and [18F]Flotaza, which are used for imaging tau and amyloid plaques in Alzheimer's disease. These studies report that the tracers were safe and well-tolerated in their respective trials, but they do not provide information on the safety of the EAAT2 PET tracer.178911
Do I need to stop taking my current medications for the trial?Yes, you must stop taking CNS prescription drugs for three weeks before participating in the trial.
Eligibility Criteria
This trial is for adults aged 40-75 with suitable arteries for catheterization, non-smokers, not on CNS drugs for three weeks, and those who can consent or have a guardian to do so. Pregnant or breastfeeding individuals and those with certain medical devices or conditions that could affect the study's outcome are excluded.Inclusion Criteria
My arm's main arteries are suitable for a catheter procedure.
I am between 40 and 75 years old.
I do not smoke or use nicotine replacement therapies.
Exclusion Criteria
I am not pregnant.
I cannot or will not follow the study rules, or no one can consent for me.
Treatment Details
[18F]RP-115 PET/MRI or PET/CT along with MRI is being tested to see if it can detect early brain changes in Alzheimer's and frontotemporal dementia patients. This first-in-human study evaluates the safety and diagnostic capabilities of this new imaging agent.
4Treatment groups
Experimental Treatment
Group I: Cohort 2C - [18F]RP-115 in patients with FTDExperimental Treatment1 Intervention
Comparison of \[18F\]RP-115 PET binding between AD patients and age-matched cognitively normal controls and between AD and FTD
Group II: Cohort 2B - [18F]RP-115 in patients with ADExperimental Treatment1 Intervention
Comparison of \[18F\]RP-115 PET binding between AD patients and age-matched cognitively normal controls and between AD and FTD
Group III: Cohort 2A - [18F]RP-115 in age-matched controlsExperimental Treatment1 Intervention
Comparison of \[18F\]RP-115 PET binding between AD patients and age-matched cognitively normal controls and between AD and FTD
Group IV: Cohort 1 - dosimetry of [18F]RP-115 in healthy volunteersExperimental Treatment1 Intervention
Establish \[18F\]RP-115 safety in the clinic with male and female PET imaging.
Find a clinic near you
Research locations nearbySelect from list below to view details:
China Basin, UCSFSan Francisco, CA
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Who is running the clinical trial?
David WilsonLead Sponsor
Rio pharmaceuticals Inc.Collaborator
References
Development of Alzheimer's disease imaging agents for clinical studies. [2019]Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive loss of neurotransmitters, as well as acetylcholinesterase and nicotinic acetylcholine receptors in the central nervous system that leads to learning and memory deficits, among other problems. The disease is associated with increased production and accumulation extracellular amyloid plaques and neurofibrillary tangles in aging human brain, shown in postmortem exams. New methods for reliable in vivo measurement of brain therefore would be much more ideal. PET and SPECT imaging are sensitive methods for the quantitation of AD biomarkers. The development of molecular imaging agents for AD is critically important in the early diagnosis, neuropathogenesis studies and treatment of AD. A number of potential diagnostic PET and SPECT imaging agents targeting AD have been synthesized and evaluated. Although many agents showed excellent results for in vitro monitoring of the disease, there are only several radioligands with high selectivity and specificity to binding sites and appropriate pharmacokinetics, such as [11C]MP4A, [11C]PMP, [11C]nicotine, 2- or 6-[18F]fluoro-A-85380, [11C]SB-13, [11C]PIB, and [18F]FDDNP, that have been tested in AD patients. Here we review some recent progress and development of AD imaging agents using PET and SPECT in human clinical studies.
Positron emission tomography imaging in dementia. [2022]Positron emission tomography (PET) is a well-established imaging modality. Measurement of regional cerebral glucose metabolism (rCMR(glc)) using PET and [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG) has become a standard technique in both oncology and dementia research. When measuring rCMR(glc) in Alzheimer's disease (AD), characteristic reductions in rCMR(glc) are found in neocortical association areas including the posterior cingulate, precuneus, temporoparietal and frontal multimodal association regions; the primary visual cortex, sensorimotor cortex, basal ganglia and cerebellum are relatively unaffected. FDG-PET has been used in the study of mild cognitive impairment (MCI) to accurately predict the subsequent decline to AD. Impairment in rCMR(glc) may be seen in individuals at high genetic risk of AD, even before clinical symptoms are apparent. Characteristic patterns of regional hypometabolism are also seen in other degenerative dementias such as frontotemporal dementia (FTD) and dementia with Lewy bodies (DLB). The use of different radioisotopes and tracers increases the versatility of PET. Tracers adopted in dementia research include (11)C-PK-11195 and (11)C-PIB, which have been used to investigate neuroinflammation and amyloid deposition, respectively, in both AD and MCI populations. It is also possible to investigate neurotransmitter systems in dementia; targets have included the cholinergic, dopaminergic and serotonergic systems. Imaging the brains of dementia patients using PET provides important information about the brain function of these individuals that would otherwise be unavailable with other imaging modalities. PET will continue to be important in future dementia research as new tracers become available to help in the early and specific diagnosis of increasingly well-defined clinical syndromes, and assist in the assessment of new therapeutic interventions.
Radiopharmaceuticals for positron emission tomography investigations of Alzheimer's disease. [2021]Alzheimer's disease (AD) is a common degenerative neurological disease that is an increasing medical, economical, and social problem. There is evidence that a long "asymptomatic" phase of the disease exists where functional changes in the brain are present, but structural imaging for instance with magnetic resonance imaging remains normal. Positron emission tomography (PET) is one of the tools by which it is possible to explore changes in cerebral blood flow and metabolism and the functioning of different neurotransmitter systems. More recently, investigation of protein aggregations such as amyloid deposits or neurofibrillary tangles containing tau-protein has become possible. The purpose of this paper is to review the current knowledge on various (18)F- and (11)C-labelled PET tracers that could be used to study the pathophysiology of AD, to be used in the early or differential diagnosis or to be used in development of treatment and in monitoring of treatment effects.
PET/CT in diagnosis of dementia. [2022]Clinical use of positron emission tomography (PET) is now well established in neurodegenerative disorders, especially in the diagnosis of dementia. Measurement of cerebral glucose metabolism is of significant value, and it facilitates early diagnosis, appropriate differential diagnosis, and the evaluation of drug treatment in patients with dementia. In addition, tracers offer new perspectives for studying the neuropathology of underlying dementia, such as the accumulation of amyloid proteins, tau-proteins, or the presence of neuroinflammation. Finally, PET tracer studies of different neurotransmitter systems in dementia may not only increase the understanding of pathophysiologic mechanisms of the different disorders, but also improve diagnostic accuracy. In conclusion, PET imaging with different tracers offers reliable biomarkers in dementia, which can assist clinicians in the diagnosis of different dementing disorders, especially in the situation of overlapping phenotypes.
Quantification of Tau Load Using [18F]AV1451 PET. [2019]Label="PURPOSE">The tau tracer [18F]AV1451, also known as flortaucipir, is a promising ligand for imaging tau accumulation in Alzheimer's disease (AD). Most of the previous studies have quantified tau load using standardized uptake value ratios (SUVr) derived from a static [18F]AV1451 scan. SUVr may, however, be flow dependent and, especially for longitudinal studies, should be validated against a fully quantitative approach. The objective of this study was to identify the optimal tracer kinetic model for measuring tau load using [18F]AV1451.
An updated radiosynthesis of [18F]AV1451 for tau PET imaging. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">[18F]AV1451 is a commonly used radiotracer for imaging tau deposits in Alzheimer's disease (AD) and related non-AD tauopathies. Existing radiosyntheses of [18F]AV1451 require complex purifications to provide doses suitable for use in clinical imaging studies. To address this issue, we have modified the synthesis of [18F]AV1451 to use only 0.5 mg precursor, optimized the Boc-deprotection step and developed a simplified method for HPLC purification of the radiotracer.
Tau PET imaging with 18F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study. [2022]18F-PI-2620 is a PET tracer with high binding affinity for aggregated tau, a key pathologic feature of Alzheimer disease (AD) and other neurodegenerative disorders. Preclinically, 18F-PI-2620 binds to both 3-repeat and 4-repeat tau isoforms. The purpose of this first-in-humans study was to evaluate the ability of 18F-PI-2620 to detect tau pathology in AD patients using PET imaging, as well as to assess the safety and tolerability of this new tau PET tracer. Methods: Participants with a clinical diagnosis of probable AD and healthy controls (HCs) underwent dynamic 18F-PI-2620 PET imaging for 180 min. 18F-PI-2620 binding was assessed visually and quantitatively using distribution volume ratios (DVR) estimated from noninvasive tracer kinetics and SUV ratio (SUVR) measured at different time points after injection, with the cerebellar cortex as the reference region. Time-activity curves and SUVR were assessed in AD and HC subjects, as well as DVR and SUVR correlations and effect size (Cohen's d) over time. Results:18F-PI-2620 showed peak brain uptake around 5 min after injection and fast washout from nontarget regions. In AD subjects, focal asymmetric uptake was evident in temporal and parietal lobes, precuneus, and posterior cingulate cortex. DVR and SUVR in these regions were significantly higher in AD subjects than in HCs. Very low background signal was observed in HCs. 18F-PI-2620 administration was safe and well tolerated. SUVR time-activity curves in most regions and subjects achieved a secular equilibrium after 40 min after injection. A strong correlation (R2 > 0.93) was found between noninvasive DVR and SUVR for all imaging windows starting at more than 30 min after injection. Similar effect sizes between AD and HC groups were obtained across the different imaging windows. 18F-PI-2620 uptake in neocortical regions significantly correlated with the degree of cognitive impairment. Conclusion: Initial clinical data obtained in AD and HC subjects demonstrated a high image quality and excellent signal-to-noise ratio of 18F-PI-2620 PET for imaging tau deposition in AD subjects. Noninvasive quantification using DVR and SUVR for 30-min imaging windows between 30 and 90 min after injection-for example, 45-75 min-provides robust and significant discrimination between AD and HC subjects. 18F-PI-2620 uptake in expected regions correlates strongly with neurocognitive performance.
PET Agents in Dementia: An Overview. [2021]This article presents an overview of imaging agents for PET that have been applied for research and diagnostic purposes in patients affected by dementia. Classified by the target which the agents visualize, seven groups of tracers can be distinguished, namely radiopharmaceuticals for: (1) Misfolded proteins (ß-amyloid, tau, α-synuclein), (2) Neuroinflammation (overexpression of translocator protein), (3) Elements of the cholinergic system, (4) Elements of monoamine neurotransmitter systems, (5) Synaptic density, (6) Cerebral energy metabolism (glucose transport/ hexokinase), and (7) Various other proteins. This last category contains proteins involved in mechanisms underlying neuroinflammation or cognitive impairment, which may also be potential therapeutic targets. Many receptors belong to this category: AMPA, cannabinoid, colony stimulating factor 1, metabotropic glutamate receptor 1 and 5 (mGluR1, mGluR5), opioid (kappa, mu), purinergic (P2X7, P2Y12), sigma-1, sigma-2, receptor for advanced glycation endproducts, and triggering receptor expressed on myeloid cells-1, besides several enzymes: cyclooxygenase-1 and 2 (COX-1, COX-2), phosphodiesterase-5 and 10 (PDE5, PDE10), and tropomyosin receptor kinase. Significant advances in neuroimaging have been made in the last 15 years. The use of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) for quantification of regional cerebral glucose metabolism is well-established. Three tracers for ß-amyloid plaques have been approved by the Food and Drug Administration and European Medicines Agency. Several tracers for tau neurofibrillary tangles are already applied in clinical research. Since many novel agents are in the preclinical or experimental stage of development, further advances in nuclear medicine imaging can be expected in the near future. PET studies with established tracers and tracers for novel targets may result in early diagnosis and better classification of neurodegenerative disorders and in accurate monitoring of therapy trials which involve these targets. PET data have prognostic value and may be used to assess the response of the human brain to interventions, or to select the appropriate treatment strategy for an individual patient.
Development and evaluation of [18F]Flotaza for Aβ plaque imaging in postmortem human Alzheimer's disease brain. [2023]Positron emission tomographic (PET) studies of amyloid β (Aβ) accumulation in Alzheimer's disease (AD) have shown clinical utility. The aim of this study was to develop and evaluate the effectiveness of a new fluorine-18 radiotracer [18F]Flotaza (2-{2-[2-[18F]fluoroethoxy]ethoxy}ethoxy)-4'-N,N-dimethylaminoazobenzene), for Aβ plaque imaging. Nucleophilic [18F]fluoride was used in a one-step radiosynthesis for [18F]flotaza. Using post mortem human AD brain tissues consisting of anterior cingulate (AC) and corpus callosum (CC), binding affinity of Flotaza, Ki = 1.68 nM for human Aβ plaques and weak (>10-5 M) for Tau protein. Radiosynthesis of [18F]Flotaza was very efficient in high radiochemical yields (>25%) with specific activities >74 GBq/μmol. Brain slices from all AD subjects were positively immunostained with anti-Aβ. Ratio of [18F]Flotaza in gray matter AC to white matter CC was >100 in all the 6 subjects. Very little white matter binding was seen. [18F]Flotaza binding in AC strongly correlated with anti-Aβ immunostains. [18F]Flotaza is therefore a suitable fluorine-18 PET radiotracer for PET imaging studies of human Aβ plaques.
What is New in Nuclear Medicine Imaging for Dementia. [2023]Advances in the molecular biology, pathology and genetics of Alzheimer's disease (AD) and other degenerative dementias have led to the development of biomarkers specific to these diseases and radiotracers that are used in nuclear medicine. Imaging and non-imaging markers have enabled very early recognition of these diseases and have caused significant changes in their definitions. Amyloid positron emission tomography (PET) and tau PET, which are molecular imaging methods, [F18]fluorodeoxyglucose (FDG) PET showing the glucose metabolism pattern in the brain, dopamine transporter single photon emission computerized tomography (SPECT) that marks dopaminergic terminals are valuable tools for early recognition and differentiation of AD and its atypical variants, frontotemporal dementias and dementia with Lewy bodies. These imaging methods, which have different advantages over each other, have different indications for use and sometimes provide complementary information. In addition, research on radiotracers targeting neuroinflammation, astrocytes, synaptic density, and cholinergic terminals is ongoing. In this review, routinely used and newly developed nuclear imaging methods in AD and other neurodegenerative dementias, the agents used and their diagnostic features will be presented together with case examples.
Simple Synthesis of [18F] AV-45 and its Clinical Application in the Diagnosis of Alzheimer's Disease. [2023][18F] AV-45 can be produced in a simple, stable, and repeatable manner on the Tracerlab FXF-N platform using a self-editing synthetic procedure and solid-phase extraction purification method. This technique is applied to positron emission tomography (PET) imaging of Alzheimer's disease (AD) to observe its distribution and characteristics in various brain regions and its diagnostic efficiency for the disease.