Trial Summary
What is the purpose of this trial?The primary objective of this substudy is to measure the concentration and the regional brain distribution of activated brain microglia/macrophages using the PET ligand \[18F\]DPA-714 in participants enrolled in the UAB Innate and Adaptive Immunity in Parkinson's Disease (Clinical Research Core) and Longitudinal \[18F\]DPA-714 Imaging in a Parkinson Disease Cohort studies. The PET tracer \[18F\]DPA-714 binds to the 18 kDa translocator protein (TSPO, also known as the peripheral benzodiazepine receptor) in the mitochondria of activated microglia/macrophages and provides a non-invasive measure of neuroinflammation. The amount and distribution of \[18F\]DPA-714 in the brain will be correlated to clinical data acquired through the separate ongoing UAB Innate and Adaptive Immunity in Parkinson Disease (Clinical Research Core) and Longitudinal \[18F\]DPA-714 Imaging in a Parkinson Disease Cohort studies. The primary objective of this study is to determine if patients with PD have higher levels of neuroinflammation than healthy controls as measured with \[18F\]DPA-714-PET/MRI.
Is the treatment in the trial 'PET Scan with DPA-714 for Parkinson's Disease' a promising treatment?Yes, PET scans, like the one using DPA-714, are promising for Parkinson's Disease because they help doctors see changes in the brain early on. This can lead to better diagnosis and tracking of the disease, which is important for finding the right treatment.12359
What safety data exists for the PET scan with DPA-714 for Parkinson's Disease?The research does not provide direct safety data for the use of [18F]DPA-714 in Parkinson's Disease. However, it mentions the use of [18F]DPA-714 in imaging studies for neuroinflammation in Alzheimer's Disease and Parkinson's Disease, indicating its application in monitoring microglial activation. The studies focus on the effectiveness of [18F]DPA-714 as a radioligand for TSPO in neuroinflammatory conditions, but specific safety data for its use in clinical trials for Parkinson's Disease is not detailed in the provided abstracts.48101113
What data supports the idea that PET Scan with DPA-714 for Parkinson's Disease is an effective treatment?The available research does not provide direct evidence that PET Scan with DPA-714 is an effective treatment for Parkinson's Disease. Instead, it discusses the use of a similar imaging technique, 18F-DOPA PET, which is used to diagnose and understand Parkinson's Disease. This imaging helps identify changes in the brain related to the disease, but it is not a treatment itself. The research also mentions the use of 18F-DOPA PET in other conditions like brain tumors, but again, this is for diagnostic purposes rather than treatment.5671214
Do I need to stop my current medications for this trial?The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the study coordinators for more information.
Eligibility Criteria
This trial is for participants already enrolled in the UAB Neuroinflammation in Parkinson's Disease study. It's specifically for those who can undergo PET/MRI scans and are not pregnant or at risk of pregnancy. Individuals must have a certain genetic profile (high or mixed affinity binder) that allows them to bind well with the imaging agent used.Treatment Details
The substudy is testing how a PET tracer called [18F]DPA-714 distributes and concentrates in the brain, which could indicate levels of neuroinflammation in Parkinson’s patients compared to healthy individuals. The tracer binds to proteins associated with inflammation in brain immune cells.
4Treatment groups
Experimental Treatment
Group I: UDALL 5-year Follow-up CohortExperimental Treatment1 Intervention
n-67 from baseline early Parkinson's disease cohort
Group II: Metabolite Analysis CohortExperimental Treatment1 Intervention
n-5 from baseline early Parkinson's disease cohort
Group III: Baseline Cohort Healthy Controls, DPA-714-PET/MRIExperimental Treatment1 Intervention
n-105
Group IV: Baseline Cohort Early Parkinson's Disease, DPA-714-PET/MRIExperimental Treatment1 Intervention
n-100
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Research locations nearbySelect from list below to view details:
UAB Advanced Imaging FacilityBirmingham, AL
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Who is running the clinical trial?
University of Alabama at BirminghamLead Sponsor
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.
Recent advances in PET imaging for evaluation of Parkinson's disease. [2021]Parkinson's disease (PD) consists of loss of pigmented dopamine-secreting neurons in the pars compacta of the midbrain substantia nigra. These neurons project to the striatum (putamen and caudate nucleus) and their loss leads to alterations in the activity of the neural circuits that regulate movement. In a simplified model, two dopamine pathways are involved: the direct pathway, which is mediated through facilitation of the D(1) receptors, and the indirect pathway through D(2) receptors (inhibitory). Positron emission tomography (PET) tracers to image the presynaptic sites of the dopaminergic system include 6-[(18)F]FDOPA and 6-[(18)F]FMT, [(11)C]dihydrotetrabenazine, [(11)C]nomifensine and various radiolabelled cocaine derivatives. Postsynaptically, for the dopamine D(1) subtype the most commonly used ligands are [(11)C]SCH 23390 or [(11)C]NNC 112 and for the D(2) subtype [(11)C]raclopride, [(11)C]MNPA and [(18)F]DMFP. PET is a sensitive and specific non-invasive molecular imaging technique that may be helpful for evaluation of PD and its differential diagnosis from other parkinsonian syndromes.
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).
[18F]DPA-714 PET imaging of translocator protein TSPO (18 kDa) in the normal and excitotoxically-lesioned nonhuman primate brain. [2022]We aimed to characterize pharmacologically the TSPO- radioligand [(18)F]DPA-714 in the brain of healthy cynomolgus monkeys and evaluate the cellular origin of its binding in a model of neurodegeneration induced by intrastriatal injection of quinolinic acid (QA).
Current status and future challenges of brain imaging with (18)F-DOPA PET for movement disorders. [2016]Parkinson's disease (PD) is a neurodegenerative disorder (ND) due to progressive loss of dopaminergic neurons in the basal ganglia. The correct differential diagnosis of this disease with parkinsonian syndromes (PS) or with essential tremor (ET) is a diagnostic dilemma, considering that only PD is responsive to treatment with levodopa. Traditional imaging fails to diagnose PD because morphological alterations in the brain are usually detectable only at advanced stages. Single photon emission tomography (SPET) with cocaine analogues has recently been used in the early detection of PD. The fluoro-18-deoxyphenyl-alanine ((18)F-DOPA) is a positron emission tomography (PET) tracer with selective in vivo affinity to the basal ganglia, due to the specific metabolism of substantia nigra. We assessed the effective use of (18)F-DOPA PET in brain imaging in order to describe the function of presynaptic disorders of PD, PS, ET and other movement disorders compared to SPET imaging and also discussed novel radiopharmaceuticals. The role of magnetic resonance imaging (MRI) was also discussed.
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).
The role of high-field magnetic resonance imaging in parkinsonian disorders: Pushing the boundaries forward. [2022]Historically, magnetic resonance imaging (MRI) has contributed little to the study of Parkinson's disease (PD), but modern MRI approaches have unveiled several complementary markers that are useful for research and clinical applications. Iron- and neuromelanin-sensitive MRI detect qualitative changes in the substantia nigra. Quantitative MRI markers can be derived from diffusion weighted and iron-sensitive imaging or volumetry. Functional brain alterations at rest or during task performance have been captured with functional and arterial spin labeling perfusion MRI. These markers are useful for the diagnosis of PD and atypical parkinsonism, to track disease progression from the premotor stages of these diseases and to better understand the neurobiological basis of clinical deficits. A current research goal using MRI is to generate time-dependent models of the evolution of PD biomarkers that can help understand neurodegeneration and provide reliable markers for therapeutic trials. This article reviews recent advances in MRI biomarker research at high-field (3T) and ultra high field-imaging (7T) in PD and atypical parkinsonism. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
[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.
Dopamine transporter imaging with [18F]FE-PE2I PET and [123I]FP-CIT SPECT-a clinical comparison. [2020]Label="BACKGROUND" NlmCategory="BACKGROUND">Dopamine transporter (DAT) imaging may be of diagnostic value in patients with clinically suspected parkinsonian disease. The purpose of this study was to compare the diagnostic performance of DAT imaging with positron emission computed tomography (PET), using the recently developed, highly DAT-selective radiopharmaceutical [18F]FE-PE2I (FE-PE2I), to the commercially available and frequently used method with [123I]FP-CIT (FP-CIT) single-photon emission computed tomography (SPECT) in early-stage idiopathic parkinsonian syndrome (PS).
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.
Initial Results of a Phase 2 Trial of 18F-DOPA PET-Guided Dose-Escalated Radiation Therapy for Glioblastoma. [2023]Label="PURPOSE">Our previous work demonstrated that 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) positron emission tomography (PET) is sensitive and specific for identifying regions of high density and biologically aggressive glioblastoma. The purpose of this prospective phase 2 study was to determine the safety and efficacy of biologic-guided, dose-escalated radiation therapy (DERT) using 18F-DOPA PET in patients with glioblastoma.
Whole-body biodistribution and radiation dosimetry of [18F]PR04.MZ: a new PET radiotracer for clinical management of patients with movement disorders. [2023]Label="PURPOSE" NlmCategory="OBJECTIVE">[18F]PR04.MZ is a new PET imaging agent for dopamine transporters, providing excellent image quality and allowing for the evaluation of patients with movement disorders such as Parkinson's disease. The objective of this study was to evaluate the biodistribution and radiation dosimetry of [18F]PR04.MZ by serial PET imaging.
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.