[18F]FDOPA Imaging for Parkinson's Disease

Overseen By Kaitlyn Hay, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Daniel Claassen

Disqualifiers: Bioimplants, Pregnancy, Minors, Mental disability, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

40 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

Is [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. ^{1 2 3 6 7}

How 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. ^{2 4 7 8 9}

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.

Eligibility 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 have a condition that affects my body's automatic functions and may have Parkinson's, MSA, or DLB.

Exclusion Criteria

You have any kind of metal implant that could move because of the magnetic field.

Prisoners

I am under 18 years old.

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

Treatment Details

Interventions

• [18F]FDOPA
• Carbidopa
• Entacapone

Trial Overview [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.

Participant Groups

Group I: [18F]F-DOPA Experimental Treatment 3 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

Who Is Running the Clinical Trial?

Daniel Claassen

Lead Sponsor

Trials

1

Recruited

40+

Findings from Research

Using high-resolution PET/CT scans with 18F-FDOPA and 11C-raclopride, this study found that both tracers showed higher uptake in normal subjects compared to previous studies, indicating improved imaging capabilities.

The study demonstrated that 18F-FDOPA uptake in the substantia nigra can be clearly visualized, providing valuable insights for evaluating regenerative therapies in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A revisit to quantitative PET with 18F-FDOPA of high specific activity using a high-resolution condition in view of application to regenerative therapy. Akamatsu, G., Ohnishi, A., Aita, K., et al.[2017]

(S)-[18F]-FMEDOPA is a new imaging agent that shows promise for better imaging of the presynaptic dopaminergic nervous system compared to the current agent (S)-[18F]-FDOPA.

In preliminary rat studies, (S)-[18F]-FMEDOPA demonstrated a higher striatum-to-cerebellum radioactivity ratio at 180 minutes post-administration, suggesting improved efficacy for imaging purposes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Yost, Y., Conway, T.[2019]

F-18 FDOPA PET imaging shows high specificity (91%) and positive predictive value (92%) for detecting dopaminergic degeneration in patients with Parkinson's disease, indicating it is a reliable tool for diagnosis.

The study, involving 68 parkinsonian subjects, found moderate sensitivity (73%) for the imaging technique, and it received FDA approval in October 2019, highlighting its potential as a diagnostic method in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective F-18 FDOPA PET Imaging Study in Human PD. Dhawan, V., Niethammer, MH., Lesser, ML., et al.[2023]

The study compared the production of the radiotracer 6-[18F]F-L-DOPA at three clinical sites, revealing that the electrophilic synthesis method has a lower production failure rate despite being more complex, making it reliable for clinical use.

Among the nucleophilic methods, the five-step approach yielded better radiochemical results but required more sophisticated equipment, while the three-step method had lower yields but produced higher molar activity, which is crucial for certain clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GMP production of 6-[18F]Fluoro-L-DOPA for PET/CT imaging by different synthetic routes: a three center experience. Andersen, VL., Soerensen, MA., Dam, JH., et al.[2021]

In a study involving 25 participants (9 normal volunteers and 16 patients with Parkinson's disease), the researchers found that measuring striatal uptake rate constants (KiFD) provided better discrimination between groups than estimating dopa decarboxylase (DDC) activity, suggesting KiFD is a more effective marker for assessing dopaminergic function in Parkinson's disease.

Both KiFD and the estimated k3D correlated significantly with disease severity ratings, but KiFD was found to be superior for clinical and research applications, indicating it may be more useful for early diagnosis of Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical significance of striatal DOPA decarboxylase activity in Parkinson's disease. Ishikawa, T., Dhawan, V., Chaly, T., et al.[2016]

6-[18F]Fluoro-L-DOPA (FDOPA) can effectively monitor changes in the central dopaminergic system in living subjects using PET imaging, providing insights into dopamine metabolism.

In MPTP-treated monkeys, significant decreases in dopamine levels were observed, correlating with changes in FDOPA metabolites, indicating that FDOPA can reflect the functional integrity of the dopamine system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

6-[18F]fluoro-L-dopa metabolism in MPTP-treated monkeys: assessment of tracer methodologies for positron emission tomography. Melega, WP., Hoffman, JM., Schneider, JS., et al.[2019]

6-[18F]-fluorodopa (FDOPA) is an effective PET imaging agent that helps visualize presynaptic dopaminergic function in the brain, making it valuable for diagnosing Parkinson's disease and differentiating it from other forms of parkinsonism.

FDOPA can also be used to study the pharmacokinetics of L-DOPA and evaluate its effects on dopamine metabolism, enhancing our understanding of treatment responses in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[PET study using 6-[18F]-fluorodopa in Parkinson's disease]. Nagasawa, H., Tanji, H., Itoh, M., et al.[2016]

A study involving 37 patients with various grades of brain tumors demonstrated that a 3-compartment model effectively describes the kinetics of (18)F-FDOPA, revealing significant differences in uptake between high-grade and low-grade tumors.

High-grade tumors exhibited higher transport rates and distinct uptake curves compared to low-grade tumors, indicating that (18)F-FDOPA can be a useful tool for differentiating tumor grades in neurooncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-FDOPA kinetics in brain tumors. Schiepers, C., Chen, W., Cloughesy, T., et al.[2016]

The radiotracer (18)F-FDOPA is effective in diagnosing and monitoring Parkinson's disease by targeting presynaptic dopaminergic terminals in the brain, which helps in assessing disease progression and may influence drug development.

In addition to its use in Parkinson's disease, (18)F-FDOPA shows high sensitivity and accuracy in visualizing brain tumors, particularly low-grade gliomas and neuroendocrine tumors, due to its role as a precursor for neurotransmitters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Seibyl, JP., Chen, W., Silverman, DH.[2016]

References

1. Japan pubmed.ncbi.nlm.nih.gov

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]

2. United States pubmed.ncbi.nlm.nih.gov

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]

3. Germany pubmed.ncbi.nlm.nih.gov

Prospective F-18 FDOPA PET Imaging Study in Human PD. [2023]

4. England pubmed.ncbi.nlm.nih.gov

GMP production of 6-[18F]Fluoro-L-DOPA for PET/CT imaging by different synthetic routes: a three center experience. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical significance of striatal DOPA decarboxylase activity in Parkinson's disease. [2016]

6. Netherlands pubmed.ncbi.nlm.nih.gov

6-[18F]fluoro-L-dopa metabolism in MPTP-treated monkeys: assessment of tracer methodologies for positron emission tomography. [2019]

7. Japan pubmed.ncbi.nlm.nih.gov

[PET study using 6-[18F]-fluorodopa in Parkinson's disease]. [2016]

8. United States pubmed.ncbi.nlm.nih.gov

18F-FDOPA kinetics in brain tumors. [2016]

9. United States pubmed.ncbi.nlm.nih.gov

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]