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?

The trial aims to optimize an imaging test called 18F-DOPA PET/CT, which examines certain medical conditions. It focuses on patients with congenital hyperinsulinism, neuroblastoma, neuroendocrine tumors, Parkinson's disease, Lewy body dementia, and brain tumors. Participants will receive an injection of 18F-DOPA, a substance that reveals specific changes in the body during the scan. This trial suits individuals with these conditions who can comfortably lie flat during the imaging procedure. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to the validation of a potentially impactful diagnostic tool.

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-DOPA PET/CT imaging is safe for pediatric and adult patients?

Research has shown that 18F-DOPA is generally safe for humans. The FDA approved it in 2019 for assessing certain brain functions, providing extensive information on its effects in the body. Studies have found it useful for imaging conditions like Parkinson's disease and certain tumors, with reports indicating that patients usually tolerate it well.

Most side effects are mild and temporary, such as a warm sensation or a metallic taste during the scan. Serious side effects are rare. Since this study is in a later phase, 18F-DOPA has already passed several safety tests in earlier research, making it a promising option for imaging the conditions under study. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about 18F-DOPA PET/CT imaging because it offers a unique approach to diagnosing and monitoring neurological conditions like Parkinson's disease and certain types of tumors. Unlike standard imaging techniques, 18F-DOPA uses a radiopharmaceutical that targets dopamine-producing regions in the brain, providing more detailed and specific images. This could lead to earlier and more accurate diagnoses, which is crucial for effective treatment planning. Additionally, the use of furosemide injection in this protocol may enhance image clarity by reducing background noise, further improving the quality of diagnostic information.

What evidence suggests that 18F-DOPA PET/CT imaging is effective for optimizing imaging in specific patient populations?

Research has shown that 18F-DOPA PET/CT scans aid in managing certain health conditions. For patients with brain tumors, these scans prompted changes in treatment plans for 41% of cases, with most changes implemented. The scans also detect tumors that produce specific hormones. Specifically, for neuroendocrine tumors, 18F-DOPA scans show promise for improved detection and understanding. While primarily used for imaging, these findings suggest the scans play a crucial role in diagnosing and managing specific diseases. Participants in this trial will receive an intravenous injection of the investigational 18F-DOPA radiopharmaceutical to further optimize its clinical use. ^{3 6 7 8 9}

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-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 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]

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]

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]

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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22323780/

Impact of 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine PET/ ... (18)F-DOPA PET/CT changed the intended management of 41% of patients with brain tumors, and intended management changes were implemented in 75% of these.

2. mdpi.com mdpi.com/2077-0383/14/7/2168

A Practical, Short, [18F]F-DOPA PET/CT Acquisition ... Background/Objectives: Determining whether 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine positron emission tomography/computed tomography ([18F]F-DOPA PET/CT) ...

3. ar.iiarjournals.org ar.iiarjournals.org/content/anticanres/38/1/353.full-text.pdf

Clinical Value of 18F-FDOPA PET/CT With Contrast ... 6-[18F]fluoro-3,4-dihydroxy-L-phenylalanine (18F-FDOPA) has been proposed as a useful radiopharmaceutical for the imaging of catecholamine-secreting tumors. In ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5924589/

fluoro-L-phenylalanine (18F-DOPA) PET and MRI in patients ... The purpose of this study is to compare the sensitivity and specificity of 18F-DOPA-PET and MRI in patients with recurrent glioma. Thirteen ...

5. jnm.snmjournals.org jnm.snmjournals.org/content/49/4/573

6-l-18F-Fluorodihydroxyphenylalanine PET in ... In none of 8 patients with surgically proven hyperparathyroidism, 18F-DOPA uptake was noted, whereas ultrasound or 99mTc-MIBI imaging results were positive (57) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9123108/

Prospective F-18 FDOPA PET Imaging Study in Human PD Our prospective study demonstrates high specificity and moderate sensitivity of F-18 FDOPA PET for PD. We received NDA approval in October 2019.

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK23043/

L-3,4-Dihydroxy-6-[18F]fluorophenylalanine - NCBI - NIH 6-[ 18 F]Fluoro-L-DOPA (FDOPA) is a radiolabeled analog of L-DOPA used to evaluate the central dopaminergic function of pre-synaptic neurons using positron ...

8. mdpi.com mdpi.com/1424-8247/17/9/1215

The Role of 18F-FDOPA PET Imaging Computed Tomography (CT) imaging plays a crucial role in the diagnosis and management of glioblastoma, a highly aggressive primary brain tumor.

9. researchgate.net researchgate.net/publication/353058214_18_F-6-Fluoro-l-Dopa_PETCT_Imaging_of_Congenital_Hyperinsulinism

(PDF) 18 F-6-Fluoro-l-Dopa PET/CT Imaging of Congenital ... 18F-6-fluoro-l-dopa PET/CT is the method of choice for the detection and localization of a focal lesion of hyperinsulinism. Surgical resection ...