The purpose of this study is to evaluate the safety and pancreas imaging properties of 18F-AV-133.

The primary objective of this protocol is to address the feasibility for further development of the VMAT2-binding compound 18F-AV-133 as a diagnostic radiopharmaceutical in the field of diabetes. Specifically, this study will evaluate 18F-AV-133 imaging in patients with type 1 diabetes, patients with type 2 diabetes and in healthy controls in order to:

1. Obtain information regarding the safety of 18F-AV-133 in these populations;
2. Determine whether uptake, distribution, or clearance of 18F-AV-133 in the pancreas differs between subjects with predicted reduced beta cell mass (patients with type 1 or type 2 diabetes of long duration) and normal beta cell mass (healthy volunteers);
3. Evaluate the PET imaging pharmacokinetics of 18F-AV-133 in abdominal organs of healthy control subjects and patients with type 1 or type 2 diabetes;
4. Obtain preliminary information regarding the appropriate time window for optimal PET imaging of 18F-AV-133 in the pancreas post-administration for type 1, type 2, and normal healthy individuals;
5. Obtain preliminary information regarding an appropriate reference tissue for evaluating the PET imaging results of 18F-AV-133 in the pancreas; and
6. Evaluate the imaging properties of 18F-AV-133 in the pancreas relative to the brain in a subset of subjects.

Patients with type 1 diabetes may be enrolled if they meet all of the following criteria:

• Are males or females between 18 and 70 years of age, inclusive;
• Have a diagnosis of type 1 diabetes mellitus as defined by ADA criteria; diabetes onset younger than age 21, duration >5 years; Insulin dose requirements ≤ 0.8 units/kg/day;
• HbA1c level ≥ 5% and ≤ 8%;
• Have fasting C-Peptide < 0.1 ng/ml;
• Have a BMI between 18 and 32 kg/m2;
• Able to tolerate PET imaging;
• In the judgment of the physician, are capable of fasting 4-6 hours prior to screening and Day 1 imaging procedures; and
• Give informed consent.

Patients with type 2 diabetes may be enrolled if they meet all of the following criteria:

• Are males or females between 18 and 70 years of age, inclusive;
• Must have been diagnosed with type 2 diabetes for more than five years;
• HbA1c level ≥ 5% and ≤ 8%;
• Have a BMI between 18 and 32 kg/m2;
• Glucose > 200 mg/dl on Mixed Meal Tolerance Test at screening visit;
• Able to tolerate PET imaging;
• In the judgment of the physician, are capable of fasting 4-6 hours prior to screening and Day 1 imaging procedures; and
• Give informed consent.

Healthy volunteers may be enrolled if they meet all of the following criteria:

• Are males or females between 18 and 70 years of age, inclusive;
• Have no history of type 1 or type 2 diabetes in a first degree relative;
• Fasting blood glucose ≤ 100 mg/dL;
• HbA1c level ≤ 6%;
• Normal Mixed Meal Tolerance test at screening visit;
• BMI between 18 and 32 kg/m2;
• Able to tolerate PET imaging;
• In the judgment of the physician, are capable of fasting 4-6 hours prior to screening and Day 1 imaging procedures; and
• Give informed consent.

Subjects will be excluded from enrollment if they meet any of the following 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;
• Use medications known to affect dopaminergic function, including MAO inhibitors, tetrabenazine, or levodopa;
• Recent (within 3 months) or current treatment with drugs influencing beta cell function or insulin sensitivity (e.g. glucocorticoids, reserpine);
• Have polycystic ovarian syndrome;
• History of movement disorder such as Parkinson's Disease, Huntington's Disease;
• Clinically significant psychiatric disease or history of psychiatric illness such as depression, bipolar disease, anxiety or schizophrenia;
• Current use (within past year) of cocaine, methamphetamine, and/or ecstasy ( MDMA, 34- methylenedioxymethamphetamine;
• Have a recent history of alcohol or substance abuse or dependence;
• Clinically significant cardiovascular disease or clinically significant abnormalities on screening ECG (including but not limited to QTc>450 msec);
• 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;
• Are women of childbearing potential who are not surgically sterile, 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 breastfeeding at screening, and must agree to take appropriate steps not to become pregnant for 30 days following the clinical trial;
• Require medications with a narrow therapeutic window (e.g., warfarin), are receiving any investigational medications, or have participated in a trial with investigational medications within the last 30 days;
• Weigh more than the manufacturer-recommended limit for the PET/CT camera being used;
• Any prior participation in other research protocols within the past month that involved radiation, with the exception of plain radiography studies (i.e., chest x-rays); and
• Have received a diagnostic or therapeutic radiopharmaceutical within the past week.