[18F]FDOPA Imaging for Parkinson's Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Daniel Claassen
Disqualifiers: Bioimplants, Pregnancy, Minors, Mental disability, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?Alpha-synucleinopathies refer to age-related neurodegenerative and dementing disorders, characterized by the accumulation of alpha-synuclein in neurons and/or glia. The anatomical location of alpha-synuclein inclusions (Lewy Bodies) and the pattern of progressive neuronal death (e.g. caudal to rostral brainstem) give rise to distinct neurological phenotypes, including Parkinson's disease (PD), Multiple System Atrophy (MSA), Dementia with Lewy Bodies (DLB). Common to these disorders are the involvement of the central and peripheral autonomic nervous system, where Pure Autonomic Failure (PAF) is thought (a) to be restricted to the peripheral autonomic system, and (b) a clinical risk factor for the development of a central synucleinopathy, and (c) an ideal model to assess biomarkers that predict phenoconversion to PD, MSA, or DLB. Such biomarkers would aid in clinical trial inclusion criteria to ensure assessments of disease- modifying strategies to, delay, or halt, the neurodegenerative process. One of these biomarkers may be related to the neurotransmitter dopamine (DA) and related changes in the substantia nigra (SN) and brainstem. \[18F\]F-DOPA is a radiolabeled substrate for aromatic amino acid decarboxylase (AAADC), an enzyme involved in the production of dopamine. Use of this radiolabeled substrate in positron emission tomography (PET) may provide insight to changes in monoamine production and how they relate to specific phenoconversions in PAF patients. Overall, this study aims to identify changes in dopamine production in key regions including the SN, locus coeruleus, and brainstem to distinguish between patients with PD, MSA, and DLB, which may provide vital information to predict conversion from peripheral to central nervous system disease.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the drug [18F]FDOPA for Parkinson's Disease?
Research shows that F-18 FDOPA PET imaging is effective in identifying Parkinson's disease by measuring dopaminergic activity, which is crucial for diagnosing and understanding the disease. Additionally, studies indicate that [18F]FDOPA provides reliable imaging results, which can help in assessing the progression of Parkinson's disease.
12345Is [18F]FDOPA safe for use in humans?
The studies on [18F]FDOPA, primarily used for imaging in Parkinson's disease, suggest it is generally safe for human use. It has been evaluated in various studies, including those submitted to the FDA, indicating its safety as an imaging agent in humans.
12467How is the drug [18F]FDOPA unique in treating Parkinson's disease?
[18F]FDOPA is unique because it is used as a radiotracer in PET imaging to evaluate presynaptic dopaminergic function in the brain, helping to diagnose Parkinson's disease and differentiate it from other conditions. Unlike typical treatments that aim to manage symptoms, [18F]FDOPA provides detailed insights into the brain's dopamine system, which is crucial for understanding the disease's progression.
34789Eligibility Criteria
This trial is for adults with a diagnosis of pure autonomic failure or those who may have Parkinson's Disease (PD), Multiple System Atrophy (MSA), or Dementia with Lewy Bodies (DLB). Healthy adults can also participate. Excluded are pregnant women, minors, prisoners, individuals with certain bioimplants, mental disabilities preventing informed consent, and those unable to follow the study protocol.Inclusion Criteria
I have been diagnosed with pure autonomic failure.
Medical examination confirming the diagnosis.
I am 18 years old or older and in good health.
+1 more
Exclusion Criteria
You have any kind of metal implant that could move because of the magnetic field.
Prisoners
I am under 18 years old.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Imaging
Participants receive [18F]F-DOPA for PET imaging to measure pre-synaptic dopamine in the brain
1 day
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after imaging
4 weeks
Participant Groups
[18F]FDOPA PET imaging is being tested to observe dopamine production in the brainstem and related areas. The goal is to distinguish between PD, MSA, DLB in patients with autonomic failure. Participants will take Carbidopa and Entacapone orally before imaging to enhance the test's accuracy.
1Treatment groups
Experimental Treatment
Group I: [18F]F-DOPAExperimental Treatment3 Interventions
All patients will receive \[18F\]F-DOPA for PET imaging to measure pre-synaptic dopamine in the brain.
[18F]FDOPA is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as [18F]F-DOPA for:
- Diagnostic imaging for neurodegenerative disorders such as Parkinson's disease, Multiple System Atrophy, and Dementia with Lewy Bodies
🇪🇺 Approved in European Union as [18F]F-DOPA for:
- Diagnostic imaging for neurodegenerative disorders such as Parkinson's disease, Multiple System Atrophy, and Dementia with Lewy Bodies
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Vanderbilt University Medical CenterNashville, TN
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Who Is Running the Clinical Trial?
Daniel ClaassenLead Sponsor
References
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.
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).
GMP production of 6-[18F]Fluoro-L-DOPA for PET/CT imaging by different synthetic routes: a three center experience. [2021]Label="BACKGROUND" NlmCategory="BACKGROUND">The radiofluorinated levodopa analogue 6-[18F]F-L-DOPA (3,4-dihydroxy-6-18F-L-phenylalanine) is a commonly employed radiotracer for PET/CT imaging of multiple oncological and neurological indications. An unusually large number of different radiosyntheses have been published to the point where two different Ph. Eur. monographs exist depending on whether the chemistry relies on electrophilic or nucleophilic radiosubstitution of appropriate chemical precursors. For new PET imaging sites wishing to adopt [18F]FDOPA into clinical practice, selecting the appropriate production process may be difficult and dependent on the clinical needs of the site.
Synthesis and preliminary evaluation of (S)-(2-[18F]fluoro-4,5-dihydroxyphenyl)-2-methyl L-alanine, (S)-[18F]-FMEDOPA, a potentially improved imaging agent for the presynaptic dopaminergic nervous system. [2019]The synthesis and preliminary rat biodistribution studies of (S)-(2-[18F]fluoro-4,5-dihydroxyphenyl)-2-methyl L-alanine, (S)-[18F]-FMEDOPA, a potentially improved imaging agent for the presynaptic dopaminergic nervous system, are reported. (S)-[18F]-FMEDOPA produces a higher striatum-to-cerebellum (S/C) radioactivity ratio than the currently used PET imaging agent, (S)-[18F]-FDOPA, does at 180 min after administration.
Clinical significance of striatal DOPA decarboxylase activity in Parkinson's disease. [2016]We performed dynamic PET studies with fluorodopa (FDOPA) in 9 normal volunteers and 16 patients with Parkinson's disease to investigate the applicability of dopa decarboxylase (DDC) activity measurements as useful markers of the parkinsonian disease process.
6-[18F]fluoro-L-dopa metabolism in MPTP-treated monkeys: assessment of tracer methodologies for positron emission tomography. [2019]6-[18F]Fluoro-L-DOPA (FDOPA) is an L-DOPA analog that is used to assess the functional integrity of central dopaminergic systems in vivo with positron emission tomography (PET). FDOPA metabolites from putamen of normal and MPTP-treated monkeys were characterized to correlate FDOPA metabolism changes with those of the endogenous dopamine system. In MPTP-lesioned putamen, 6-[18F]fluorodopamine and dopamine levels were less than 2% those of controls. Increases in endogenous dopamine metabolism were reflected by similar increases in 6-[18F]fluorodopamine metabolites. These results suggest that changes in the central dopamine system biochemistry can be monitored in vivo with FDOPA and PET.
[PET study using 6-[18F]-fluorodopa in Parkinson's disease]. [2016]6-[18F]-fluorodopa (FDOPA) was developed as an analogue of L-DOPA across the blood-brain-barrier and to carry into nigrostriatal dopaminergic neurons. PET study using FDOPA revealed presynaptic dopaminergic function in the striatum of nigrostriatal system of the human brain and many studies have performed to clarify the pathogenesis of Parkinson's disease. FDOPA is also an efficient tracer to analyze pharmacokinetics of L-DOPA by measuring radioactivities of its metabolites in the peripheral blood by HPLC and to evaluate pharmacological effects on dopamine metabolism by pretreatment of dopa decarboxylase inhibitor or COMT inhibitor. PET study using FDOPA is useful not only to diagnose Parkinson's disease but also to differentiate from parkinsonism in combination with other radioactive ligands and with other neuroimaging methods such as MRI.
18F-FDOPA kinetics in brain tumors. [2016]L-3,4-Dihydroxy-6-(18)F-fluoro-phenyl-alanine ((18)F-FDOPA) is an amino acid analog used to evaluate presynaptic dopaminergic neuronal function. Evaluation of tumor recurrence in neurooncology is another application. Here, the kinetics of (18)F-FDOPA in brain tumors were investigated.
3,4-dihydroxy-6-[18f]-fluoro-L-phenylalanine positron emission tomography in patients with central motor disorders and in evaluation of brain and other tumors. [2016]The use of 3,4-dihydroxy-6-[(18)F]-fluoro-L-phenylalanine ((18)F-FDOPA) with positron emission tomography initially centered on studying central motor disorders and evaluating patients with Parkinsonian symptoms, based on its uptake into presynaptic dopaminergic terminals in the putamen and caudate nuclei of the brain. The roles of this tracer have since expanded to include monitoring disease progression, potentially contributing to drug development, and even questioning the current gold standard for making the diagnosis of Parkinson's disease. As with some other amino acids, (18)F-FDOPA has also been effective for visualizing brain tumors, either at time of diagnosis or when monitoring for recurrence, with high sensitivity and overall accuracy. (18)F-FDOPA may be especially useful for imaging patients with low-grade gliomas, as well in the evaluation of patients with neuroendocrine tumors such as carcinoid and pheochromocytoma, in which its role as a precursor for amine neurotransmitter/neurohormones serves as a basis for its differential uptake.