18F-DOPA PET/CT Imaging Optimization

Overseen By Jonathan Abele, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Alberta

Disqualifiers: Pregnancy, Weight >225 kg, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

800 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

A single centre non-randomized, non-blinded phase III prospective cohort study of 18F-DOPA PET/CT imaging in specific patient populations: 1. Pediatric patients (less than 18 years old) with congenital hyperinsulinism. 2. Pediatric patients (less than 18 years old) with neuroblastoma. 3. Pediatric (less than 18 years old) or Adult patients (18 or older) with known or clinically suspected neuroendocrine tumor. 4. Adult patients (18 or older) with a clinical suspicion of Parkinson's disease or Lewy body dementia. 5. Pediatric (less than 18 years old) or Adult patients (18 or older) with brain tumors. Image optimization (the primary study objective) and gallbladder activity pattern (the secondary objective) will be evaluated.

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.

Is 18F-DOPA PET/CT imaging safe for humans?

18F-DOPA has been used safely for many years in imaging for Parkinson's disease and neuroendocrine tumors. Some formulations may cause a mild burning sensation at the injection site, but studies have shown that new formulations are well-tolerated in cell and animal tests. ^{1 2 3 4 5}

How does the drug 18F-DOPA differ from other treatments for neuroendocrine tumors?

18F-DOPA is unique because it is a radiotracer used in PET/CT imaging to detect and manage neuroendocrine tumors by mimicking the natural amino acid L-DOPA, which is taken up by specific transporters in the body. This allows for precise imaging of tumor activity, which is different from traditional treatments that may not provide such detailed visualization. ^{1 5 6 7 8}

What data supports the effectiveness of the drug 18F-DOPA in the clinical trial?

Research shows that 18F-DOPA PET imaging is useful for detecting and managing brain tumors, movement disorders, and neuroendocrine tumors. It has been used effectively in imaging for Parkinson's disease and carcinoid tumors, helping to locate tumors more accurately than some traditional methods. ^{1 2 5 9 10}

Who Is on the Research Team?

Jonathan Abele, MD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

This trial is for children and adults with certain conditions like congenital hyperinsulinism, neuroendocrine tumors, brain tumors, Parkinson's disease or Lewy body dementia. It excludes pregnant individuals, those over 225 kg, patients who can't lie flat for the scan duration or give consent, and young kids who can't be sedated safely.

Inclusion Criteria

I am under or over 18 and may have a neuroendocrine tumor.

I am an adult suspected to have Parkinson's disease or Lewy body dementia.

I am under 18 and have been diagnosed with congenital hyperinsulinism.

Exclusion Criteria

I cannot lie flat for 20-30 minutes.

You do not have a way for the study drug to be given through a vein.

Unable to obtain consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Imaging and Assessment

Participants receive an 18F-DOPA PET/CT scan to assess image optimization and gallbladder activity patterns

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

1 month

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• 18F-DOPA
• Furosemide Injection

Trial Overview The study tests how well a PET/CT imaging technique works using an injection of Furosemide and a radioactive drug called 18F-DOPA. The goal is to optimize images for better diagnosis in various diseases including brain tumors and Parkinson's.

How Is the Trial Designed?

Group I: 18F-DOPA injection Experimental Treatment 2 Interventions

All enrolled participants will receive an intravenous injection of the investigational 18F-DOPA radiopharmaceutical

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Published Research Related to This Trial

F-DOPA PET/CT imaging shows minimal physiological uptake in the brain, except for the basal ganglia, while significant uptake is observed in the liver, pancreas, and urinary system, indicating its potential utility in diagnosing various conditions.

Incidental findings of F-DOPA uptake occurred in 5.5% of patients, often linked to inflammation or benign tumors, highlighting the importance of correlating imaging results with other diagnostic methods for accurate interpretation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-DOPA PET/CT Physiological Distribution and Pitfalls: Experience in 215 Patients. Calabria, FF., Chiaravalloti, A., Jaffrain-Rea, ML., et al.[2018]

The new 18F-labeled l-DOPA analogue, [18F]FPDOPA, was successfully synthesized with a good yield and specific activity, making it a promising candidate for PET imaging of tumors.

In vivo studies showed that [18F]FPDOPA accumulates significantly in various tumor types, indicating its potential as a more effective PET tracer for brain tumors compared to the commonly used [18F]FDG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosynthesis and biological evaluation of N-(2-[18F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine as a PET tracer for oncologic imaging. Tang, C., Nie, D., Tang, G., et al.[2018]

The new formulations of 6-[18F]fluoro-l-dihydroxyphenylalanine (18F-DOPA) maintain chemical stability at a pH of 5.0, which eliminates the need for pH adjustment before injection, potentially reducing discomfort for patients.

In vitro tests on various cell lines and in vivo studies in rats indicate that these new formulations are well-tolerated, suggesting they are safe for further evaluation in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical development of novel lactate-based 6-fluoro-l-DOPA formulations. Denora, N., Lopedota, A., de Candia, M., et al.[2017]

In a study of 53 patients with metastatic carcinoid tumors, (18)F-DOPA PET demonstrated a diagnostic sensitivity of 100% for detecting tumors, outperforming conventional imaging methods like somatostatin-receptor scintigraphy (SRS) and CT.

(18)F-DOPA PET not only detected more lesions than combined SRS and CT but also showed significantly higher sensitivity in region-based and individual-lesion analyses, suggesting it could be a superior option for tumor localization and monitoring treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Staging of carcinoid tumours with 18F-DOPA PET: a prospective, diagnostic accuracy study. Koopmans, KP., de Vries, EG., Kema, IP., et al.[2022]

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]

A meta-analysis of three randomized controlled trials with 1021 patients found that the once-daily extended-release (ER) formulation of pramipexole has similar adverse event rates compared to the standard immediate-release (IR) formulation in patients with Parkinson's disease.

Common adverse events such as nausea, somnolence, dizziness, and dyskinesia showed no significant differences between the two formulations, indicating that both options are similarly safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of the adverse events associated with extended-release versus standard immediate-release pramipexole in Parkinson disease. Shen, Z., Kong, D.[2022]

A novel synthesis method for (18)F-DOPA produced a product with a specific activity 1000 times higher than the conventional method, which could enhance its effectiveness in imaging neuroendocrine tumors.

Despite the higher specific activity, both high-specific-activity (18)F-DOPA-H and low-specific-activity (18)F-DOPA-L showed similar uptake and imaging properties in tumor models, indicating that the new synthesis method is both simpler and allows for lower doses without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo biodistribution of no-carrier-added 6-18F-fluoro-3,4-dihydroxy-L-phenylalanine (18F-DOPA), produced by a new nucleophilic substitution approach, compared with carrier-added 18F-DOPA, prepared by conventional electrophilic substitution. Kuik, WJ., Kema, IP., Brouwers, AH., et al.[2022]

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 study found that L-type amino acid transporters (LAT1 and LAT2) are significantly overexpressed in pheochromocytoma (PHEO) and medullary thyroid carcinoma (MTC) compared to normal tissues, with LAT1 showing a particularly strong increase in PHEO (15.1-fold).

This overexpression of LAT1 provides a molecular basis for the increased uptake of 18F-FDOPA in these tumors, which can enhance the effectiveness of PET imaging in clinical management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overexpression of L-Type Amino Acid Transporter 1 (LAT1) and 2 (LAT2): Novel Markers of Neuroendocrine Tumors. Barollo, S., Bertazza, L., Watutantrige-Fernando, S., et al.[2019]

In a study of 59 patients with newly diagnosed or recurrent gliomas, (18)F-FDOPA PET imaging showed significantly higher uptake in high-grade tumors compared to low-grade tumors, indicating its potential as a noninvasive marker for tumor grading.

The study found a strong correlation between (18)F-FDOPA uptake and tumor proliferation in newly diagnosed gliomas, suggesting that this imaging technique could help assess tumor activity and aggressiveness, although this correlation was not present in recurrent tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation of 6-18F-fluoro-L-dopa PET uptake with proliferation and tumor grade in newly diagnosed and recurrent gliomas. Fueger, BJ., Czernin, J., Cloughesy, T., et al.[2016]

Citations

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

18F-DOPA PET/CT Physiological Distribution and Pitfalls: Experience in 215 Patients. [2018]

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

Radiosynthesis and biological evaluation of N-(2-[18F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine as a PET tracer for oncologic imaging. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmaceutical development of novel lactate-based 6-fluoro-l-DOPA formulations. [2017]

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

Staging of carcinoid tumours with 18F-DOPA PET: a prospective, diagnostic accuracy study. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

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

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

Meta-analysis of the adverse events associated with extended-release versus standard immediate-release pramipexole in Parkinson disease. [2022]

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

In vivo biodistribution of no-carrier-added 6-18F-fluoro-3,4-dihydroxy-L-phenylalanine (18F-DOPA), produced by a new nucleophilic substitution approach, compared with carrier-added 18F-DOPA, prepared by conventional electrophilic substitution. [2022]

8. 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]

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

Overexpression of L-Type Amino Acid Transporter 1 (LAT1) and 2 (LAT2): Novel Markers of Neuroendocrine Tumors. [2019]

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

Correlation of 6-18F-fluoro-L-dopa PET uptake with proliferation and tumor grade in newly diagnosed and recurrent gliomas. [2016]