A Trial of 18F-AV-133 Positron Emission Tomography (PET)

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.