Positron Emission Tomography (PET) Imaging of Pancreatic Beta-Cell Mass in Healthy and Type 1 Diabetic Patients

Study Overview
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Brief Summary
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Pancreatic Islet beta-cells are responsible for synthesizing and secreting appropriate amounts of insulin to regulate blood glucose levels. One factor in the development of diabetes is the loss of beta-cells. Developing treatments to prevent or restore islet beta-cell mass (BCM) in diabetic patients is hampered by a lack of methods for the non-invasive imaging of these cells. This study is designed to evaluate a radiolabeled compound that binds to the pancreatic islet. The investigators will test the ability of one promising imaging compound, 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-DTBZ), to measure the amount of pancreatic islet beta-cells in patients with long-standing type-1 diabetes and in age-weight-matched healthy control subjects.

Official Title
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Quantitative PET Imaging of Pancreatic Beta-cell Mass in Healthy and Type 1 Diabetic Patients With 18F-FP-DTBZ (AV-133)

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: 18F-FP-DTBZ (18F-AV-133)
* Biological: Arginine-hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Type 1 diabetes may be enrolled if they meet all of the following criteria: Have a diagnosis of Type 1 diabetes mellitus defined by ADA criteria or judgment of physician; diabetes onset younger than age 18, duration >5 years Have fasting C-Peptide ≤ 0.1 ng/ml BMI between 18 and 29 kg/m2 Able to tolerate PET and MR imaging No metal implants No claustrophobia Healthy volunteers may be enrolled if they meeting all of the following criteria: Have no history of Type 1 diabetes Fasting blood glucose ≤ 100 mg/dL Negative islet autoantibody testing BMI between 18 and 29 kg/m2 Able to tolerate PET and MR imaging No history of previous allergic reactions to drugs No metal implants No claustrophobia Exclusion Criteria: Clinically significant renal dysfunction; Clinically significant liver dysfunction as determined by history, physical examination, and standard liver function testing at screening (AST, ALT, Total/Direct Bilirubin, Alkaline Phosphatase); Coagulopathy; History of allergic reactions to any drug Current use of any medications except for insulin for Type 1 diabetes Clinically significant cardiovascular disease or clinically significant abnormalities on screening ECG (including but not limited to QTc>450 msec); Clinically significant psychiatric disease; Clinically significant pulmonary, renal or hepatic impairment or cancer, have clinically significant infectious disease, including AIDS or HIV infection, or previous positive test for hepatitis B, hepatitis C, HIV-1, or HIV-2; subjects will be asked about this. No testing will be performed. Have a history of alcohol or substance abuse or dependence; Are women of childbearing potential not refraining from sexual activity or not using adequate contraception. Women must not be pregnant (negative serum β-HCG at the time of screen) or lactating at screening, and must agree to take appropriate steps not to become pregnant during the study and for 30 days following the study. Currently receiving any investigational medications, or have participated in a trial with investigational medications within the last 30 days. Have received a diagnostic or therapeutic radiopharmaceutical within 7 days prior to participation in this study. Claustrophobia Metal implants (pace-maker, artificial joints, non-removable body piercings)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Type 1 diabetic subjects<br>Patients with Type 1 diabetes who have a diagnosis of Type 1 diabetes mellitus defined by ADA criteria or judgment of physician | Drug: 18F-FP-DTBZ (18F-AV-133)<br>* The subjects will receive a single IV bolus of approximately 10 mCi 18F-AV-133.(Injection will contain no more than 25 µg of non-radiolabeled 19F-AV-133).<br>Biological: Arginine-hydrochloride<br>* A bolus injection of 5g of 10% arginine-hydrochloride will be given over a period of 1 minute.<br>|
| Healthy control subjects<br>Age-weight-BMI matched to the subjects with type-1 diabetes | Drug: 18F-FP-DTBZ (18F-AV-133)<br>* The subjects will receive a single IV bolus of approximately 10 mCi 18F-AV-133.(Injection will contain no more than 25 µg of non-radiolabeled 19F-AV-133).<br>Biological: Arginine-hydrochloride<br>* A bolus injection of 5g of 10% arginine-hydrochloride will be given over a period of 1 minute.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET-determined pancreatic islet beta-cell mass |  | 150 minutes post-dose of imaging agent | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin secretion response following an acute arginine-stimulus test |  | Six minutes following administration of arginine challange | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, islet, pancreas, beta cell mass, PET imaging, FPDTBZ, arginine stimulus test