a trial of 18f-av-133 positron emission tomography (pet)

Conditions: Type 1 Diabetes; Type 2 Diabetes

Summary: 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.

Eligibility criteria:
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.