Fluorodopa F 18 for Congenital Hyperinsulinism

Overseen By Deborah Rafferty, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Cook Children's Health Care System

Must be taking: Anti-hypoglycemics

Disqualifiers: Pregnancy, Breastfeeding, Allergy to Fluorodopa, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

250 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients should have failed standard medical therapy, which includes medications like diazoxide or octreotide, before being considered for surgery.

What data supports the effectiveness of the drug Fluorodopa F 18 for congenital hyperinsulinism?

Research shows that Fluorodopa F 18 PET imaging is useful for diagnosing congenital hyperinsulinism by accurately identifying the location of insulin-producing cells in the pancreas, which helps in managing the condition. ^{1 2 3 4 5}

Is Fluorodopa F 18 safe for humans?

The research articles do not provide specific safety data for Fluorodopa F 18 in humans, but they discuss its use in imaging for conditions like congenital hyperinsulinism and brain tumors. ^{1 3 5 6 7}

How is the drug Fluorodopa F 18 unique for treating congenital hyperinsulinism?

Fluorodopa F 18 is unique because it is used in PET/CT imaging to accurately distinguish between focal and diffuse forms of congenital hyperinsulinism, which helps in precisely localizing the affected areas. This imaging technique is currently the first-line method for this purpose and has no recognized competitors among available imaging techniques. ^{3 4 5 8 9}

What is the purpose of this trial?

Low blood sugars are known to cause brain damage in newborn babies. One of the most common causes of low blood sugars persisting beyond the new born period is a condition called congenital hyperinsulinism (HI). This is a disease whereby the pancreas secretes too much insulin and causes low blood sugars. Twenty to forty percent of these babies will have brain damage. There are two forms of this disease. In one form only a small part of the pancreas makes too much insulin (focal HI) and in the other, the whole pancreas make too much insulin (diffuse HI). Another very similar disease is insulinoma which occurs after birth, but also causes hyperinsulinism. If a surgeon could know which part of the pancreas has the focal lesion he could remove it and cure the patient. The purpose of this study is to investigate whether a new investigational drug called Fluorodopa F 18, when used with a PET scan, can find the focal lesion and guide the surgeon to remove it, thus curing the patient and preventing further brain damage.

Research Team

Dr. Paul Thornton

Principal Investigator

Cook Children's Health Care System

Eligibility Criteria

This trial is for patients with congenital hyperinsulinism (HI) or insulinoma, who are being treated at the Cook Children's Congenital Hyperinsulinism Center. It's suitable for those without genetic proof of diffuse HI, considering surgery to cure their condition. Pregnant women, those allergic to Fluorodopa F 18, without an HI diagnosis, and nursing mothers not pausing breastfeeding post-injection are excluded.

Inclusion Criteria

My genetic tests for HI disease are either negative or not done, but I want surgery for a potential cure.

My doctor recommends surgery for my severe hypoglycemia because medications haven't worked.

I am being treated for hyperinsulinism at Cook Children's by an endocrinologist.

Exclusion Criteria

Nursing mothers who are unwilling to discontinue breastfeeding their infant for 48 hours after Fluorodopa F 18 injection

I am allergic to Fluorodopa F 18.

Patients who are pregnant

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo Fluorodopa F 18 PET combined with CT to produce pancreatic images

1 day

1 visit (in-person)

Surgery

Participants may undergo partial or complete pancreatectomy based on imaging results

up to 1 month

Follow-up

Participants are monitored for safety and effectiveness after surgery

4 weeks

Treatment Details

Interventions

• Fluorodopa F 18

Trial Overview The study tests if a new drug called Fluorodopa F 18 can help locate the exact area in the pancreas causing too much insulin when used with a PET scan. This could enable surgeons to remove just that part and potentially cure the patient.

Participant Groups

Group I: Pancreatic Imaging with Fluorodopa F 18 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Cook Children's Health Care System

Lead Sponsor

Trials

11

Recruited

5,001,000+

Findings from Research

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]

The introduction of 6-(18)F-fluoro-L-dopa ((18)F-FDOPA) PET and PET/CT imaging has enhanced the ability to study neuroendocrine tumors (NETs) and pancreatic beta-cell hyperplasia, providing a valuable tool for diagnosis and management.

Institutions with expertise in treating NETs can significantly benefit from (18)F-FDOPA PET/CT, as it aids in guiding therapy to achieve better tumor control and maximize cytoreduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-FDOPA: a multiple-target molecule. Minn, H., Kauhanen, S., Seppänen, M., et al.[2016]

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]

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]

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]

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]

In a study of 16 patients with hyperinsulinaemic hypoglycaemia (HH), (18)F-FDOPA PET/CT imaging with carbidopa premedication successfully detected insulinomas in 73% of patients with confirmed diagnoses, demonstrating improved detection rates compared to previous methods without premedication.

The use of carbidopa significantly reduced background pancreatic activity, allowing for better visualization of tumors, with a detection rate of 53% for primary lesions across all patients with HH, highlighting the importance of this premedication in enhancing the efficacy of (18)F-FDOPA PET/CT imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-FDOPA PET/CT imaging of insulinoma revisited. Imperiale, A., Sebag, F., Vix, M., et al.[2018]

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]

A new method for producing 6-[18F]fluoro-L-dopa, a compound used in medical imaging, was developed using a reaction between [18F]fluorine gas and L-dopa in liquid hydrogen fluoride.

This synthesis method yields 3 mCi of 6-[18F]fluoro-L-dopa from 100 mCi of [18F]F2, demonstrating an efficient production process for this important radiotracer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatic radiofluorination with [18F]fluorine gas: 6-[18F]fluoro-L-dopa. Firnau, G., Chirakal, R., Garnett, ES.[2013]

References

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

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

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

18F-FDOPA: a multiple-target molecule. [2016]

3. England pubmed.ncbi.nlm.nih.gov

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

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

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

5. 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]

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

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

7. Germany pubmed.ncbi.nlm.nih.gov

18F-FDOPA PET/CT imaging of insulinoma revisited. [2018]

8. 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]

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

Aromatic radiofluorination with [18F]fluorine gas: 6-[18F]fluoro-L-dopa. [2013]