[18F]FDOPA Imaging for Parkinson's Disease

Overseen By Kaitlyn O'Rourke, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates how a special imaging technique using [18F]FDOPA, a radiotracer used in PET scans, can clarify dopamine's role in neurodegenerative conditions like Parkinson's disease, Multiple System Atrophy, and Dementia with Lewy Bodies. Researchers aim to identify changes in dopamine production in the brain that could indicate the progression of these conditions. The trial is open to individuals diagnosed with pure autonomic failure or those experiencing autonomic failure with possible signs of Parkinson's, MSA, or DLB. It may also include healthy adults as a comparison group. Participants must not have certain medical implants or conditions that might interfere with the imaging process. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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 prior data suggests that [18F]FDOPA is safe for PET imaging in Parkinson's Disease?

Research has shown that [18F]FDOPA is generally safe. In past studies, it demonstrated a good safety record, with few reports of negative side effects. [18F]FDOPA is used in PET scans to visualize brain areas related to dopamine production, aiding in the understanding of diseases like Parkinson's.

Overall, evidence suggests that [18F]FDOPA is well-tolerated, with no major safety concerns reported. This makes it a promising option for those considering participation in a clinical trial involving this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

[18F]FDOPA is unique because it offers a new way to visualize dopamine activity in the brain, which is crucial for understanding Parkinson's disease. Unlike standard treatments that focus on managing symptoms with medications like Levodopa or dopamine agonists, [18F]FDOPA is used for PET imaging to measure pre-synaptic dopamine levels directly. This approach provides researchers with a clearer picture of how Parkinson's affects the brain's dopamine system, potentially leading to earlier and more accurate diagnoses. Researchers are excited about this technique because it could pave the way for more personalized and effective treatment strategies in the future.

What evidence suggests that [18F]FDOPA imaging is effective for Parkinson's Disease?

Research has shown that a special type of brain scan called [18F]FDOPA PET imaging helps track Parkinson's disease and other movement disorders. In this trial, all participants will receive [18F]FDOPA for PET imaging to measure pre-synaptic dopamine in the brain. This scan monitors disease progression by revealing changes in dopamine production. [18F]FDOPA highlights areas where dopamine is active, making disease-related changes easier to see. This imaging method commonly identifies which brain parts are affected by diseases like Parkinson's. It provides important insights into dopamine level changes, aiding in predicting the development of conditions such as Parkinson's, Multiple System Atrophy, and Dementia with Lewy Bodies. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. imaging-cro.biospective.com imaging-cro.biospective.com/resources/fdopa-parkinsons-disease-clinical-trials

[18F]DOPA PET in Parkinson's Disease Clinical Trials [18F]DOPA PET is used to monitor disease progression & response to therapeutic intervention in Parkinson's disease & movement disorders clinical trials.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2946843/

Long-Term Clinical and 18F-FDOPA PET Outcomes - PMC At the end of the blinded phase, we found a significant increase in putamen uptake on 18F-fluorodopa (18F-FDOPA) PET reflecting the viability of the grafts.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4284201/

Fluoro-L-dopa uptake in Parkinson's disease 6-[18F]-Fluoro-L-dopa (FDOPA) has been widely used as a biomarker for catecholamine synthesis, storage, and metabolism—its intense uptake in the striatum, ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2019/200655Orig1s000MultidisciplineR.pdf

Multi-Discipline Review - accessdata.fda.gov Fluorodopa F 18 Injection is a radioactive diagnostic agent indicated for use in positron emission tomography (PET) to visualize dopaminergic ...

5. imrpress.com imrpress.com/journal/JIN/19/3/10.31083/j.jin.2020.03.196/htm

[18F] FDOPA PET may confirm the clinical diagnosis of ... The present study aimed to assess the feasibility of evaluating cardiac sympathetic denervation in Parkinson's disease patients using L-3,4-dihydroxy-6-[18F] ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4749509/

The sensitivity and specificity of F-DOPA PET in a ... In this study, we aim to illustrate our local experience to determine the accuracy of 18 F-DOPA PET for diagnosis of PD.

7. go.drugbank.com go.drugbank.com/drugs/DB13848

Fluorodopa (18F): Uses, Interactions, Mechanism of Action Fluorodopa F 18 is indicated for use with positron emission tomography (PET) to visualize dopaminergic nerve terminals in the striatum.

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1111/jnc.14016

Comparative assessment of 6‐[18F]fluoro‐L‐m‐tyrosine ... The aim of this study was to perform a quantitative comparison of brain images obtained in 6-hydroxydopamine (6-OHDA) lesioned rats using two ...