Fluorodopa F 18 for Congenital Hyperinsulinism

Recruiting in Palo Alto (17 mi)

Overseen by Dr. Paul Thornton

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Cook Children's Health Care System

Must be taking: Anti-hypoglycemics

Disqualifiers: Pregnancy, Breastfeeding, Allergy to Fluorodopa, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

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.

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}

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

Trial 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 (Radiopharmaceutical)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Cook Children's Medical Center Fort Worth, TX

Who Is Running the Clinical Trial?

Cook Children's Health Care System Lead Sponsor

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] Studies have reported the applications of F-dihydroxyphenylalanine (F-DOPA) PET in patients with congenital hyperinsulinism (CHI). The aim of this study was to systematically review and perform a meta-analysis of published data on the diagnostic role of F-DOPA PET in patients with CHI.

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

18F-FDOPA: a multiple-target molecule. [2016] Although 6-(18)F-fluoro-L-dopa ((18)F-FDOPA) has been available to study the striatal dopaminergic system for more than 2 decades, the full potential of the tracer was not realized before the introduction of (18)F-FDOPA PET and PET/CT to image a variety of neuroendocrine tumors (NETs) and pancreatic beta-cell hyperplasia. Together with receptor-based imaging, (18)F-FDOPA offers a formerly unforeseen means to assist in the management of NETs and infants with persistent hyperinsulinemic hyperplasia. Institutions with special expertise in surgical, oncologic, and radiologic therapeutic modalities for NETs derive the highest benefit from (18)F-FDOPA PET/CT. (18)F-FDOPA-guided therapy may add to NET control by ensuring maximal cytoreduction.

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

Strengths and limitations of using 18fluorine-fluorodihydroxyphenylalanine PET/CT for congenital hyperinsulinism. [2019] 18fluorine-fluorodihydroxyphenylalanine (FDOPA) PET/CT is currently the first-line imaging technique to distinguish between focal and diffuse forms of congenital hyperinsulinism (CHI) and to accurately localize focal forms. However, this technique has a number of limitations, mainly the very small size of focal forms or inversely a very large focal form mimicking a diffuse form, and misinterpretation of physiologic uptake masking hot spots or inversely mimicking focal forms. The other limitation is the limited availability of the radiopharmaceutical. FDOPA PET/CT has no recognized competitor to date among the available morphologic and functional imaging techniques. Other potential approaches using specific tracers for positron emission tomography (PET) are discussed, using radiopharmaceuticals specific for &#946; cell mass or targeting somatostatin receptors. These radiopharmaceuticals can be labeled with gallium-68, a PET emitter readily available in PET centers equipped with 68Ge/68Ga generators.

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] We aimed to elucidate the accuracy and limitations of [(18)F]-fluoro-L-dihydroxyphenylalanine ([(18) F]DOPA) positron emission tomography (PET) for Japanese patients with congenital hyperinsulinism. Although [(18)F]DOPA PET is reported to be useful for precisely localizing the focal form of congenital hyperinsulinism, previous reports are mostly from European and North American centres.

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] Fluorine-18-L-dihydroxyphenylalanine positron emission tomography (18F-FDOPA PET) imaging is increasingly used in the workup of neuroendocrine tumors. It has been shown to be an accurate tool in the diagnosis of congenital hyperinsulinism, but limited information is available on its value in adult disease. OBJECTIVE, PATIENTS, AND DESIGN: The objective of this study was to review our experience with 18F-FDOPA PET imaging in six consecutive patients with hyperinsulinemic hypoglycemia (HH) (four solitary insulinomas, one diffuse beta-cell hyperplasia, one malignant insulinoma). 18F-FDOPA uptake was also evaluated in 37 patients (43 procedures) without HH or other pancreatic neuroendocrine tumors, which acted as a control group.

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

18F-FDOPA kinetics in brain tumors. [2016] L-3,4-Dihydroxy-6-(18)F-fluoro-phenyl-alanine ((18)F-FDOPA) is an amino acid analog used to evaluate presynaptic dopaminergic neuronal function. Evaluation of tumor recurrence in neurooncology is another application. Here, the kinetics of (18)F-FDOPA in brain tumors were investigated.

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

18F-FDOPA PET/CT imaging of insulinoma revisited. [2018] (18)F-FDOPA PET imaging is increasingly used in the work-up of patients with neuroendocrine tumours. It has been shown to be of limited value in localizing pancreatic insulin-secreting tumours in adults with hyperinsulinaemic hypoglycaemia (HH) mainly due to (18)F-FDOPA uptake by the whole pancreatic gland. The objective of this study was to review our experience with (18)F-FDOPA PET/CT imaging with carbidopa (CD) premedication in patients with HH in comparison with PET/CT studies performed without CD premedication in an independent population.

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] 6-18F-fluoro-L-3,4-dihydroxyphenylalanine (18F-FDOPA) PET is a useful tool in the clinical management of pheochromocytoma (PHEO) and medullary thyroid carcinoma (MTC). 18F-FDOPA is a large neutral amino acid biochemically resembling endogenous L-DOPA and taken up by the L-type amino acid transporters (LAT1 and LAT2). This study was conducted to examine the expression of the LAT system in PHEO and MTC.

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

Aromatic radiofluorination with [18F]fluorine gas: 6-[18F]fluoro-L-dopa. [2013] A new synthesis is described for the routine production of 3,4-dihydroxy-6-[18F]fluoro-phenyl-L-alanine (6-[18F]fluoro-L-dopa). The reaction between [18F]fluorine gas and 3,4-dihydroxyphenyl-L-alanine (L-dopa) in liquid hydrogen fluoride gave 2-, 5-, and 6-[18F]fluoro-L-dopa. 6-[18F]Fluoro-L-dopa was isolated by reverse-phase high-pressure liquid chromatography. From 100 mCi [18F]F2, the method produces 3 mCi of 6-[18F]fluoro-L-dopa at the end of synthesis.