FDOPA/PET Imaging for Congenital Hyperinsulinism

(DOPA PET Trial)

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Miguel Pampaloni

Must be taking: Diazoxide, Octreotide

Must not be taking: Nifedipine, Glucagon

Disqualifiers: Hepatic insufficiency, Renal insufficiency

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

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

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

Compensation: Varies

Number of Visits: 1

50 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this project is to determine the role of FDOPA/PET as a pre-operative diagnostic imaging procedure for differentiating focal and diffuse forms of congenital hyperinsulinism and locating focal lesions in the pancreas to guide surgical resection.

Will I have to stop taking my current medications?

Yes, you will need to stop taking your current medications in time to have a washout period (time without taking certain medications) before the scheduled PET scan.

What data supports the effectiveness of the treatment 18F-Fluoro Dopa Imaging for congenital hyperinsulinism?

Research shows that 18F-DOPA PET imaging is effective in identifying the specific areas in the pancreas causing congenital hyperinsulinism, especially the focal form, which can then be surgically removed to potentially cure the condition. ^{1 2 3 4 5}

Is FDOPA/PET imaging safe for humans?

The research does not provide specific safety data for FDOPA/PET imaging, but it is commonly used in medical settings for diagnosing conditions like congenital hyperinsulinism, suggesting it is generally considered safe for human use. ^{1 2 6 7 8}

How is FDOPA/PET imaging different from other treatments for congenital hyperinsulinism?

FDOPA/PET imaging is unique because it helps to accurately identify and locate focal forms of congenital hyperinsulinism, which can be treated with surgery. This imaging technique is the first-line method for distinguishing between focal and diffuse forms of the condition, unlike other treatments that do not provide such precise localization. ^{1 6 9 10 11}

Research Team

Miguel Hernandez Pampaloni, MD, PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for anyone, especially infants aged 0-6 months with uncontrolled hypoglycemia due to congenital hyperinsulinism, who have normal liver and kidney function. It's not for those on certain third-line hyperinsulinism medications or with liver/kidney insufficiency.

Inclusion Criteria

I am an infant aged 0-6 months, the typical age for this condition.

Able to withdraw medications in time to wash out prior to the scheduled PET scan

I have uncontrolled low blood sugar after pancreas surgery.

Exclusion Criteria

I am taking third-line medications like nifedipine or glucagon for hyperinsulinism.

I have liver or kidney problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo FDOPA PET/CT imaging to differentiate focal and diffuse forms of congenital hyperinsulinism and locate focal lesions in the pancreas

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

Treatment Details

Interventions

• 18F-Fluoro Dopa Imaging

Trial Overview The study tests if a special PET scan using FDOPA can tell apart different types of congenital hyperinsulinism and pinpoint lesions in the pancreas before surgery.

Participant Groups

Group I: Single Arm, Experimental Treatment 1 Intervention

Patients with clinically diagnosed congenital hyperinsulinism

Who Is Running the Clinical Trial?

Miguel Pampaloni

Lead Sponsor

Trials

2

Recruited

60+

Findings from Research

In a study of 17 Japanese infants with congenital hyperinsulinism, [(18)F]DOPA PET showed limited accuracy in diagnosing the condition, with only 7 out of 17 cases aligning with molecular diagnoses when assessed by simple inspection.

The diagnostic accuracy improved significantly when using a quantitative measure called the 'Pancreas Percentage', leading to consistent results in 10 out of 17 patients, indicating that this method enhances the effectiveness of [(18)F]DOPA PET for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic accuracy of [¹⁸F]-fluoro-L-dihydroxyphenylalanine positron emission tomography scan for persistent congenital hyperinsulinism in Japan. Masue, M., Nishibori, H., Fukuyama, S., et al.[2022]

F-DOPA PET and PET/CT have shown high sensitivity (88%) and specificity (79%) in diagnosing congenital hyperinsulinism (CHI) based on a meta-analysis of 10 studies involving 181 patients.

The accuracy of F-DOPA PET and PET/CT in detecting CHI is supported by a high area under the receiver-operating characteristic curve (0.92), indicating these imaging techniques are reliable diagnostic tools, although clinicians should be aware of potential false-positive and false-negative results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic role of 18F-dihydroxyphenylalanine positron emission tomography in patients with congenital hyperinsulinism: a meta-analysis. Yang, J., Hao, R., Zhu, X.[2016]

18F-6-fluoro-l-dopa PET/CT is the preferred imaging technique for detecting and localizing focal lesions in infants and children with congenital hyperinsulinism, which causes severe hypoglycemia.

Surgical removal of these focal lesions, guided by PET/CT imaging, can potentially cure the condition with minimal pancreatectomy, reducing the risk of brain damage associated with persistent hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-6-Fluoro-l-Dopa PET/CT Imaging of Congenital Hyperinsulinism. States, LJ., Davis, JC., Hamel, SM., et al.[2022]

The 18F-DOPA PET examination was highly effective in detecting hyperplastic lesions in patients with congenital hyperinsulinism, identifying focal lesions in 12 out of 14 cases, and accurately locating the lesions in 91.7% of those cases.

Surgical resection of the identified focal hyperplastic lesions in the pancreas was performed safely in all cases under 2 years of age, demonstrating that this approach can be an effective treatment for congenital hyperinsulinism, although intraoperative pathologic examination is recommended to confirm lesion distribution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Congenital hyperinsulinism treated by surgical resection of the hyperplastic lesion which had been preoperatively diagnosed by 18F-DOPA PET examination in Japan: a nationwide survey. Kanamori, Y., Watanabe, T., Yorifuji, T., et al.[2019]

In a study of 19 children with congenital hyperinsulinism, 18F-DOPA PET/CT successfully identified focal forms of the disease in 10 participants, allowing for targeted surgical resection in 4 cases, leading to complete recovery.

The imaging technique demonstrated a significant difference in uptake between focal lesions and normal pancreatic tissue, indicating its effectiveness in localizing focal CHI for surgical planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of 18F-DOPA PET/CT in the diagnosis of the congenital focal form of hyperinsulinism in children. Chroustova, D., Trnka, J., Pudlac, A., et al.[2021]

Congenital hyperinsulinism is a major cause of hypoglycemia in infants, and identifying focal hyperinsulinism can lead to a cure through partial pancreatectomy.

Using FDOPA-PET imaging allows for effective functional mapping of hyperinsulinism by highlighting areas of the pancreas that utilize L-DOPA at higher rates, aiding in the localization of the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorine-18 DOPA-PET and PET/CT Imaging in Congenital Hyperinsulinism. Houseni, M., Chamroonrat, W., Zhuang, H., et al.[2016]

In a study involving six patients with hyperinsulinemic hypoglycemia, 18F-FDOPA PET imaging was only positive in one case, indicating its limited effectiveness in detecting insulinomas and beta-cell hyperplasia in adults.

The pancreatic uptake of 18F-FDOPA was not significantly different between patients with hyperinsulinemic hypoglycemia and a control group, suggesting that this imaging technique may not reliably localize insulin-secreting tumors in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited value of 18F-F-DOPA PET to localize pancreatic insulin-secreting tumors in adults with hyperinsulinemic hypoglycemia. Tessonnier, L., Sebag, F., Ghander, C., et al.[2019]

In a 55-day-old boy with hypoglycemia, 18F-DOPA PET/CT imaging successfully identified a focal lesion in the pancreas associated with congenital hyperinsulinism.

The imaging also revealed a left thoracic paraspinal neuroblastoma, indicating that 18F-DOPA PET/CT can be effective in detecting multiple conditions in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroblastoma Shown on 18F-DOPA PET/CT Performed to Evaluate Congenital Hyperinsulinism. O'Brien, SR., States, LJ., Zhuang, H.[2023]

FDOPA PET/CT is the primary imaging method for identifying and localizing focal congenital hyperinsulinism (CHI), but it has limitations such as difficulty in detecting small focal forms and potential misinterpretation due to physiological uptake.

Alternative PET imaging techniques using gallium-68 labeled tracers targeting β cell mass or somatostatin receptors may offer more accessible and effective options for diagnosing CHI, addressing the limitations of FDOPA PET/CT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strengths and limitations of using 18fluorine-fluorodihydroxyphenylalanine PET/CT for congenital hyperinsulinism. Montravers, F., Arnoux, JB., Ribeiro, MJ., et al.[2019]

The use of (18)F-DOPA PET scans can detect focal forms of congenital hyperinsulinism, but the uptake of (18)F-DOPA does not necessarily indicate the insulin-secreting ability of pancreatic lesions, as shown in a case study of a boy with a mutation in the ABCC8 gene.

The patient experienced spontaneous resolution of hypoglycemia without significant insulin release, suggesting that clinical remission can occur without the death of abnormal β-cells, highlighting a potential functional recovery mechanism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lasting 18F-DOPA PET uptake after clinical remission of the focal form of congenital hyperinsulinism. Yorifuji, T., Hosokawa, Y., Fujimaru, R., et al.[2017]

The (18)F-DOPA-PET-CT scan is effective in distinguishing between diffuse and focal congenital hyperinsulinism (CHI) in infants, with accurate results in 14 out of 19 children studied.

However, the scan was inaccurate in locating or sizing the focal lesions in 36% of cases, indicating that while it is a useful tool, intraoperative histologic confirmation is necessary to ensure complete resection of the lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The predictive value of preoperative fluorine-18-L-3,4-dihydroxyphenylalanine positron emission tomography-computed tomography scans in children with congenital hyperinsulinism of infancy. Zani, A., Nah, SA., Ron, O., et al.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

Diagnostic accuracy of [¹⁸F]-fluoro-L-dihydroxyphenylalanine positron emission tomography scan for persistent congenital hyperinsulinism in Japan. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Diagnostic role of 18F-dihydroxyphenylalanine positron emission tomography in patients with congenital hyperinsulinism: a meta-analysis. [2016]

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

18F-6-Fluoro-l-Dopa PET/CT Imaging of Congenital Hyperinsulinism. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Congenital hyperinsulinism treated by surgical resection of the hyperplastic lesion which had been preoperatively diagnosed by 18F-DOPA PET examination in Japan: a nationwide survey. [2019]

5. Spain pubmed.ncbi.nlm.nih.gov

The role of 18F-DOPA PET/CT in the diagnosis of the congenital focal form of hyperinsulinism in children. [2021]

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

Fluorine-18 DOPA-PET and PET/CT Imaging in Congenital Hyperinsulinism. [2016]

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

Limited value of 18F-F-DOPA PET to localize pancreatic insulin-secreting tumors in adults with hyperinsulinemic hypoglycemia. [2019]

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

Neuroblastoma Shown on 18F-DOPA PET/CT Performed to Evaluate Congenital Hyperinsulinism. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Strengths and limitations of using 18fluorine-fluorodihydroxyphenylalanine PET/CT for congenital hyperinsulinism. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Lasting 18F-DOPA PET uptake after clinical remission of the focal form of congenital hyperinsulinism. [2017]

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

The predictive value of preoperative fluorine-18-L-3,4-dihydroxyphenylalanine positron emission tomography-computed tomography scans in children with congenital hyperinsulinism of infancy. [2016]