Evaluation of 18F-FP-DTBZ Pancreatic PET Scanning as a Tool to Measure Beta Cell Mass

Diabetes results when the insulin secretory capacity of the beta cell population is lost or
severely compromised.Plasma insulin levels have been used as a surrogate marker of beta cell
mass (BCM) but insulin levels often do not correlate well. A "gold standard of measurement"
to obtain BCM would be of great value. The aim of the proposed study is to evaluate an islet
imaging technique using PET scanning to directly measure BCM and thus provide valuable
information for monitoring disease progress and response to therapy in people with diabetes
and in people at high risk for diabetes. Type 1 diabetes (T1DM) occurs when the beta cells
are selectively destroyed by a T cell mediated autoimmune process. People at high risk for
developing T1DM, such as first degree relatives of patients with T1DM, can sometimes be
identified before the disease develops by measuring autoantibodies to beta cells, however
this test is neither sensitive nor specific. Little is known about the natural history of
BCM, turnover and cell lifetime, or the course of inflammation in diabetes. This is
principally because the pancreas is a highly heterogeneous organ that is difficult to biopsy
without significant complications, and BCM only comprises 1 to 2% of the total volume.
Accurate assessment of BCM in human diabetes is limited to autopsy studies, which usually
suffer from inadequate clinical information; thus, the development of non-invasive means of
BCM measurement could be important for interventional therapies of T1DM, islet
regeneration/stem cell therapy and islet transplantation.

Inclusion Criteria:

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

1. Are males or females between 18 and 70 years of age, inclusive

2. Have a diagnosis of type 1 diabetes mellitus as defined by the American Diabetes
Association (ADA) criteria or by diagnosed as per their endocrinologist;
duration >5 years; Insulin dose requirements <0.8 units/kg/day

3. HbA1c level between 5% and 8.5%

4. Have fasting C-Peptide < 0.1 ng/ml

5. Have a body mass index (BMI) between 18 and 32 kg/m2

6. Able to tolerate PET imaging

7. In the judgment of the physician, are capable of fasting 4 to 6 hours prior to
screening and Day 1 imaging procedures

8. Give informed consent

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

1. Are males or females between 18 and 70 years of age, inclusive

2. Have no history of type 1 or type 2 diabetes in a first degree relative

3. Fasting blood glucose less than 100 mg/dL

4. HbA1c level less than 6%

5. Normal Mixed Meal Tolerance test at screening visit

6. BMI between 18 and 32 kg/m2

7. Able to tolerate PET imaging

8. In the judgment of the physician, are capable of fasting 4 to 6 hours prior to
screening and Day 1 imaging procedures, and

9. Give informed consent

Exclusion Criteria:

- Potential participants must not have any of the following exclusion criteria:

1. Clinically significant renal dysfunction

2. Clinically significant liver dysfunction as determined by history, physical
examination, and standard liver function testing at screening (aspartate
aminotransferase (AST), alanine aminotransferase (ALT), Total/Direct Bilirubin,
Alkaline Phosphatase)

3. Coagulopathy

4. Use medications known to affect dopaminergic function, including monoamine
oxidase (MAO) inhibitors, tetrabenazine, or levodopa

5. Recent (within 3 months) or current treatment with drugs influencing beta cell
function or insulin sensitivity (e.g. glucocorticoids, reserpine) medications
known to affect dopaminergic function, including MAO inhibitors, tetrabenazine,
or levodopa

6. Have polycystic ovarian syndrome

7. History of movement disorder such as Parkinson's Disease, Huntington's Disease

8. Clinically significant psychiatric disease or history of psychiatric illness
such as depression, bipolar disease, anxiety or schizophrenia

9. Current use (within past year) of cocaine, methamphetamine, and/or ecstasy
(3,4methylenedioxymethamphetamine (MDMA))

10. Have a recent history of alcohol or substance abuse or dependence

11. Clinically significant cardiovascular disease or clinically significant
abnormalities on screening electrocardiogram (ECG) (including but not limited to
QTc > 450 msec)

12. Clinically significant pulmonary, renal or hepatic impairment, or cancer

13. Have clinically significant infectious disease, including acquired immune
deficiency syndrome (AIDS) or human immunodeficiency virus (HIV) infection or
previous positive test for hepatitis B, hepatitis C, HIV1, or HIV2

14. Are women of childbearing potential not refraining from sexual activity or not
using adequate contraception.

Women must not be pregnant (negative serum human chorionic gonadotropin (hCG) at
the time of screen) or breastfeeding at screening, and must agree to take
appropriate steps not to become pregnant during for 30 days following the
clinical trial

15. 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

16. Weigh more than the manufacturer recommended limit for the PET/computed
tomography (CT) camera being used

17. 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

18. Have received a diagnostic or therapeutic radiopharmaceutical within the past
week