Trial Summary
What is the purpose of this trial?The overall goal of this protocol is to investigate \[18F\]DPA-714 binding in prodromal and early manifest Parkinson's Disease (PD) and to determine the baseline and change from baseline in \[18F\]DPA-714 binding in PD participants during a 24-month interval.
Primary Objectives
* To compare \[18F\]DPA-714 binding in prodromal and manifest PD and healthy volunteers.
* To determine the longitudinal change in \[18F\]DPA-714 during a 24-month interval for prodromal and early initially untreated PD participants.
Secondary Objectives
* To evaluate the correlation between baseline \[18F\]DPA-714 and PPMI clinical and biomarker outcomes.
* To evaluate the correlation between the longitudinal change of \[18F\]DPA-714 and PPMI clinical and biomarker outcomes
* To acquire safety data following injection of \[18F\]DPA-714
Is the treatment in the trial 'PET Imaging for Parkinson's Disease' a promising treatment?PET imaging is a promising tool for studying Parkinson's Disease because it helps doctors see changes in the brain related to the disease. It can show how active certain brain cells are and help track the progression of the disease. This can be useful for diagnosing Parkinson's Disease and evaluating how well treatments are working.12589
What safety data exists for [18F]DPA714 in Parkinson's Disease treatment?The provided research does not directly address safety data for [18F]DPA714 in Parkinson's Disease treatment. However, it mentions the use of [18F]DPA714 for imaging microglial activation in Parkinson's Disease and Alzheimer's Disease models, suggesting its application in studying neuroinflammation. No specific safety concerns or adverse effects are reported in the studies mentioned.34678
What data supports the idea that PET Imaging for Parkinson's Disease is an effective treatment?The available research shows that PET imaging, specifically using F-18 FDOPA, is effective in diagnosing Parkinson's Disease. It has been submitted for FDA approval, indicating its reliability in identifying the disease. The studies highlight its sensitivity and accuracy in detecting Parkinson's compared to other methods. Although the research primarily focuses on its diagnostic value, the effectiveness of F-18 FDOPA PET imaging in accurately assessing the condition suggests its potential usefulness in treatment planning.2351011
Do I have to stop taking my current medications for this trial?The trial protocol does not specify whether you need to stop taking your current medications. However, participants must not have started symptomatic treatment for Parkinson's Disease at the time of enrollment or during the first 2 years of participation.
Eligibility Criteria
This trial is for individuals with early-stage or prodromal Parkinson's Disease, as well as healthy volunteers. Participants will be monitored over a 24-month period to track changes in their condition.Treatment Details
[18F]DPA-714, an imaging compound, is being tested through IV administration to see how it binds in the brain of those with Parkinson's compared to healthy people and how this binding changes over two years.
2Treatment groups
Experimental Treatment
Group I: Prodromal and manifest (PD) participantsExperimental Treatment1 Intervention
Group II: Healthy participantsExperimental Treatment1 Intervention
Find a clinic near you
Research locations nearbySelect from list below to view details:
UABBirmingham, AL
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Who is running the clinical trial?
University of Alabama at BirminghamLead Sponsor
Michael J. Fox Foundation for Parkinson's ResearchCollaborator
References
Motor disturbance and brain functional imaging in Parkinson's disease. [2018]18F-Dopa positron emission tomography (PET) provides a sensitive means of quantitating the loss of nigrostriatal dopaminergic fibres in Parkinson's disease and so can be used to diagnose its presence and to objectively follow the rate of disease progression. It can also be used, in principle, to determine the efficacy of putative neuroprotective agents and has already been extensively used to monitor the viability of striatal transplants of fetal mesencephalic tissue. Loss of dopaminergic projections produces significant changes in the patterns of both resting and activated cortical function. H2(15)O PET activation studies have suggested that the akinesia of Parkinson's disease is associated with failure to activate the supplementary motor and dorsal prefrontal areas, brain regions particularly involved in motor preparation and decision making. Activation of these cortical areas can be restored by administering dopaminergic medication, implanting the striatum with fetal mesencephalic tissue, and by pallidotomy. This article reviews the insight that PET studies have provided into the pathophysiology of Parkinson's disease.
Clinical Significance of F-18 FP-CIT Dual Time Point PET Imaging in Idiopathic Parkinson's Disease. [2021]The purpose of this study was to investigate the diagnostic value of dual time point F-18 FP-CIT PET imaging in idiopathic Parkinson's disease (PD).
A revisit to quantitative PET with 18F-FDOPA of high specific activity using a high-resolution condition in view of application to regenerative therapy. [2017]Label="OBJECTIVE" NlmCategory="OBJECTIVE">With the advent of regenerative/cell therapy for Parkinson's disease (PD), 18F-FDOPA has drawn new attention as a biomarker of the therapeutic that cannot be evaluated with radiopharmaceuticals for dopamine transporter. Since most previous 18F-FDOPA PET studies were carried out many years ago with a PET scanner of lower resolution and with 18F-FDOPA of low specific activity synthesized from 18F-F2, we used a newer PET/CT scanner with a high-resolution condition and 18F-FDOPA synthesized from 18F-F- to re-evaluate this technique on normal subjects and patients with PD, together with D2 receptor imaging with 11C-raclopride (RAC).
[18F]AV-1451 binding to neuromelanin in the substantia nigra in PD and PSP. [2022]This study investigated binding of [18F]AV-1451 to neuromelanin in the substantia nigra of patients with Parkinson's disease (PD) and progressive supranuclear palsy (PSP). [18F]AV-1451 is a positron emission tomography radiotracer designed to bind pathological tau. A post-mortem study using [18F]AV-1451 discovered off-target binding properties to neuromelanin in the substantia nigra. A subsequent clinical study reported a 30% decrease in [18F]AV-1451 binding in the midbrain of PD patients. A total of 12 patients and 10 healthy age-matched controls were recruited. An anatomical MRI and a 90-min PET scan, using [18F]AV-1451, were acquired from all participants. The standardized uptake value ratio (SUVR) from 60 to 90 min post-injection was calculated for the substantia nigra, using the cerebellar cortex as the reference region. The substantia nigra was delineated using automated region of interest software. An independent samples ANOVA and LSD post hoc testing were used to test for differences in [18F]AV-1451 SUVR between groups. Substantia nigra SUVR from 60 to 90 min was significantly greater in HC compared to both PSP and PD groups. Although the PD group had the lowest SUVR, there was no significant difference in substantia nigra uptake between PD and PSP. [18F]AV-1451 may be the first PET radiotracer capable of imaging neurodegeneration of the substantia nigra in parkinsonisms. Further testing must be done in PD and atypical parkinsonian disorders to support this off-target use of [18F]AV-1451.
VMAT2 imaging agent, D6-[18F]FP-(+)-DTBZ: Improved radiosynthesis, purification by solid-phase extraction and characterization. [2020]Label="OBJECTIVES">Recently, a deuterated tracer, D6-[18F]FP-(+)-DTBZ, 9-O-hexadeutero-3-[18F]fluoropropoxyl-(+)-dihydrotetrabenazine ([18F]9), targeting vesicular monoamine transporter 2 (VMAT2) in the central nervous system, was reported as a useful imaging agent for the diagnosis of Parkinson's disease (PD). The production of [18F]9 was optimized and simplified by using solid-phase extraction (SPE) purification.
Imaging of dopamine transporters in Parkinson disease: a meta-analysis of 18 F/123 I-FP-CIT studies. [2021]Label="OBJECTIVE"> 18 F-FP-CIT and 123 I-FP-CIT are widely used radiotracers in molecular imaging for Parkinson's disease (PD) diagnosis. Compared with 123 I-FP-CIT, 18 F-FP-CIT has superior tracer kinetics. We aimed to conduct a meta-analysis to assess the efficacy of using 18 F-FP-CIT positron emission tomography (PET) and 123 I-FP-CIT single-photon emission computed tomography (SPECT) of dopamine transporters in patients with PD in order to provide evidence for clinical decision-making.
PET Imaging for Dynamically Monitoring Neuroinflammation in APP/PS1 Mouse Model Using [18F]DPA714. [2020]Background: In the pathogenesis of Alzheimer's disease (AD), microglia play an increasingly important role. Molecular imaging of neuroinflammatory targeting microglia activation and the high expression of 18-kDa translocator protein (TSPO) has become a hot topic of research in recent years. Dynamic monitoring neuroinflammation is crucial for discovering the best time point of anti-inflammatory therapy. Motivated by this, Positron emission tomography (PET) imaging in an APP/PS1 mouse model of AD, using 18F-labeled DPA-714 to monitor microglia activation and neuroinflammation, were performed in this paper. Methods: We prepared [18F]DPA714 and tested the biological characteristics of the molecular probe in normal mice. To obtain a higher radiochemical yield, we improved the [18F]-fluorination conditions in the precursor dosage, reaction temperature, and synthesis time. We performed [18F]DPA714 PET scanning on APP/PS1 mice at 6-7, 9-10, 12-13, and 15-16 months of age, respectively. The same experiments were conducted in Wild-type (Wt) mice as a control. Referring to the [18F]DPA714 concentrated situation in the brain, we performed blocking experiments with PK11195 (1 mg/kg) in 12-13-months-old APP/PS1 mice to confirm the specificity of [18F]DPA714 for TSPO in the APP/PS1 mice. Reconstructed brain PET images, fused with the Magnetic Resonance Imaging (MRI) template atlas, and the volumes of interests (VOIs) of the hippocampus and cortex were determined. The distribution of [18F]DPA714 in the brain tissues of 15-16-months-old APP/PS1 and Wt mice were studied by immunofluorescence staining. Results: Through the reaction of 18F, with 2 mg precursor dissolved in 300 ul acetonitrile at 105°C for 10 min, we obtained the optimal radiochemical yield of 42.3 ± 5.1% (non-decay correction). Quantitative analysis of brain PET images showed that the [18F]DPA714 uptake in the cortex and hippocampus of 12-13-months-old APP/PS1 mice was higher than that of the control mice of the same age (cortex/muscle: 2.77 ± 0.13 vs. 1.93 ± 0.32, p = 0.0014; hippocampus/muscle: 3.33 ± 0.10 vs. 2.10 ± 0.35, p = 0.0008). The same significant difference was found between 15- and 16-months-old APP/PS1 mice (cortex/muscle: 2.64 ± 0.14 vs. 1.86 ± 0.52, p=0.0159; hippocampus/muscle: 2.89 ± 0.53 vs. 1.77 ± 0.48, p = 0.0050). Immunofluorescence staining showed that the activation of microglia and the level of TSPO expression in the cortex and hippocampus of APP/PS1 mice were significantly higher than Wt mice. Conclusion: [18F]DPA714, a molecular probe for targeting TSPO, showed great potential in monitoring microglia activation and neuroinflammation, which can be helpful in discovering the best time point for anti-inflammatory therapy in AD.
Increased microglial activation in patients with Parkinson disease using [18F]-DPA714 TSPO PET imaging. [2021]Label="INTRODUCTION">Increasing evidence suggests that neuroinflammation is active in Parkinson disease (PD) and contributes to neurodegeneration. This process can be studied in vivo with PET and radioligands targeting TSPO, upregulated in activated microglia. Initial PET studies investigating microglial activation in PD with the [11C]-PK11195 have provided inconclusive results. Here we assess the presence and distribution of neuroinflammatory response in PD patients using [18F]-DPA714 and to correlate imaging biomarkers to dopamine transporter imaging and clinical status.
Molecular Imaging of Neurodegenerative Parkinsonism. [2021]Advances in molecular PET imaging of neurodegenerative parkinsonism are reviewed with focus on neuropharmacologic radiotracers depicting terminals of selectively vulnerable neurons in these conditions. Degeneration and losses of dopamine, norepinephrine, serotonin, and acetylcholine imaging markers thus far do not differentiate among the parkinsonian conditions. Recent studies performed with [18F]fluorodeoxyglucose PET are limited by the need for automated image analysis tools and by lack of routine coverage for this imaging indication in the United States. Ongoing research engages use of novel molecular modeling and in silico methods for design of imaging ligands targeting these specific proteinopathies.
Amino Acid PET Imaging with 18F-DOPA in the evaluation of Pediatric Brain Tumors. [2022]Although MRI is the workhorse of brain tumor initial evaluation and follow-up, there is a growing amount of data recommending the incorporation of amino-acid PET imaging at different stages of the management of these patients. Recent nuclear medicine and neuro-oncology clinical practice recommendations support the use of amino-acid imaging in brain tumor imaging. Considering 18F-DOPA is FDA approved for the evaluation of parkinsonian syndromes, it could be used clinically for other valuable clinical indications such as brain tumor evaluations. This value seems to be well established in adults and has growing evidence for its use in pediatrics as well. We offer to present four pediatric brain tumor cases imaged with 18F-DOPA and review the literature.
Prospective F-18 FDOPA PET Imaging Study in Human PD. [2023]We present the findings of our final prospective study submitted to the U.S. Food and Drug Administration (FDA) for New Drug Application (NDA) approval for the use of 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine (F-18 FDOPA) positron emission tomography (PET) imaging for Parkinson's disease (PD). The primary aim was to determine the sensitivity, specificity, and predictive values of F-18 FDOPA PET in parkinsonian patients with respect to clinical standard-of-truth (SOT). Secondary outcomes included the inter-rater reliability, and correlation of quantitative measures for PET with dopaminergic status.