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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new drug, Fluorodopa F 18, can help doctors locate and remove the problematic part of the pancreas in babies with congenital hyperinsulinism (HI). HI causes the pancreas to produce excessive insulin, leading to dangerously low blood sugar. The trial aims to prevent brain damage by curing the condition through surgery. Ideal participants are babies or children with HI who cannot be safely managed with standard treatments and require surgery to avoid severe low blood sugar episodes. As a Phase 1 trial, this research seeks to understand how this new treatment works in people, offering participants the chance to be among the first to receive this innovative drug.

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 prior data suggests that Fluorodopa F 18 is safe for use in pancreatic imaging?

Research shows that Fluorodopa F 18 is used in PET scans to detect problem areas in the pancreas for conditions like congenital hyperinsulinism. It is already approved for imaging certain nerve endings, indicating it has undergone safety testing in humans.

Studies have found that using Fluorodopa F 18 in PET scans for patients with hyperinsulinism effectively identifies parts of the pancreas that produce excess insulin. Although specific safety data for this use is limited, its approval for other imaging purposes suggests it is generally safe.

Since this trial is in an early phase, it focuses on assessing safety and effectiveness. Researchers closely monitor for any side effects to ensure participant safety. Prospective participants should discuss any concerns with the research team to understand the potential risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Fluorodopa F 18 is unique because it offers a new way to visualize pancreatic function in patients with congenital hyperinsulinism. Unlike traditional treatments that primarily aim to manage blood sugar levels, Fluorodopa F 18 is a radiotracer used in PET scans to help pinpoint areas of the pancreas that are overproducing insulin. Researchers are excited about this approach because it could lead to more accurate diagnoses and potentially guide more effective, targeted treatments, minimizing the need for invasive procedures like surgery.

What evidence suggests that Fluorodopa F 18 is effective for congenital hyperinsulinism?

This trial will use Fluorodopa F 18 for pancreatic imaging in participants with congenital hyperinsulinism (HI). Studies have shown that combining Fluorodopa F 18 with a PET scan effectively identifies specific problem areas in the pancreas for individuals with HI. This method boasts nearly 95% accuracy, correctly identifying affected areas in the pancreas most of the time. This accuracy is crucial, as it aids surgeons in removing the problematic part, potentially curing the patient and preventing brain damage. Research indicates that Fluorodopa F 18 is already used for this purpose in regions such as Europe and Australia. This technique is not only promising but has also become a preferred method in many clinical settings. ^{1 6 7 8 9}

Who Is on the Research Team?

Dr. Paul Thornton

Principal Investigator

Cook Children's Health Care System

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/34230074/

18F-6-Fluoro-l-Dopa PET/CT Imaging of Congenital ...

18 F-6-fluoro-l-dopa PET/CT is the method of choice for the detection and localization of a focal lesion of hyperinsulinism.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00674440

Utility of [F-18] fluoroDOPA for Neonatal Hyperinsulinism

In this study, researchers will test the possibility of using PET with F-DOPA in the diagnosis of children with hyperinsulinism. Official Title. Localization of ...

3.

researchgate.net

researchgate.net/publication/357549433_A_Reliable_Automated_Synthesis_of_6-18FFluoro-L-DOPA_and_the_Clinical_Application_on_the_Imaging_of_Congenital_Hyperinsulinism_of_Infants

(PDF) A Reliable Automated Synthesis of 6-[18F]Fluoro-L ...

6-[ ¹⁸ F]fluoro-L-DOPA is a radiotracer widely used in the diagnosis of a range of diseases, including neuro-oncology, endocrinology, and Parkinson's disease.

4.

ejnmmipharmchem.springeropen.com

ejnmmipharmchem.springeropen.com/articles/10.1186/s41181-021-00135-y

GMP production of 6-[18F]Fluoro-l-DOPA for PET/CT imaging ...

Data from four years of [18F]FDOPA production at three different clinical sites are collected and compared. These three sites, Aarhus University ...

5.

npcf.us

npcf.us/clinical-trials/fluorodopa-f-18-in-congenital-hyperinsulinism-and-insulinoma/

Fluorodopa F 18 In Congenital Hyperinsulinism And ...

Fluorodopa F 18 PET scanning for patients with Hyperinsulinism is now established in Europe and Australia, and has close to 95% sensitivity. When linked to ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01916148

Study Details | NCT01916148 | 18F-L-Fluoro-DOPA PET ...

Patients with hyperinsulinemic hypoglycemia are at risk for neurological damage due to hypoglycemia. Early surgical intervention can be preventative. F-DOPA PET ...

7.

researchgate.net

researchgate.net/publication/236666309_Production_at_the_Curie_Level_of_No-Carrier-Added_6-F-18-Fluoro-L-Dopa

Production at the Curie Level of No-Carrier-Added 6-F-18- ...

Methods: In this paper, 2 important chemical improvements are proposed to simplify production of (18)F-FDOPA, resulting in straightforward ...

8.

chop.edu

chop.edu/research-studies/18f-dopa-petct-scan-hyperinsulinism

18F-DOPA PET/CT scan for Hyperinsulinism

This imaging test is called an F-DOPA PET scan. The F-DOPA tracer is used to highlight areas of the pancreas that make too much insulin on the PET scan images.

9.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2019/200655s000lbl.pdf

FLUORODOPA F 18 Injection - accessdata.fda.gov

F 18 Injection is a radioactive diagnostic agent indicated for use in positron emission tomography (PET) to visualize dopaminergic nerve terminals in the ...