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| Name | Class |
|---|---|
| Pfizer | INDUSTRY |
| Avid Radiopharmaceuticals | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Type 1 diabetic subjects | Patients with Type 1 diabetes who have a diagnosis of Type 1 diabetes mellitus defined by ADA criteria or judgment of physician |
| |
| Healthy control subjects | Age-weight-BMI matched to the subjects with type-1 diabetes |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 18F-FP-DTBZ (18F-AV-133) | Drug | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| PET-determined pancreatic islet beta-cell mass | 150 minutes post-dose of imaging agent |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin secretion response following an acute arginine-stimulus test | Six minutes following administration of arginine challange |
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Inclusion Criteria:
Patients with Type 1 diabetes may be enrolled if they meet all of the following criteria:
Healthy volunteers may be enrolled if they meeting all of the following criteria:
Exclusion Criteria:
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Community Sample
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| Name | Affiliation | Role |
|---|---|---|
| Gary W Cline, Ph.D. | Yale University | Principal Investigator |
| Yu-Shin Ding, Ph.D. | Yale University | Study Director |
| Kitt F Petersen, M.D. | Yale University | Study Director |
| Richard Carson, Ph.D. | Yale University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University School of Medicine, PET Center | New Haven | Connecticut | 06520 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16934687 | Background | Goswami R, Ponde DE, Kung MP, Hou C, Kilbourn MR, Kung HF. Fluoroalkyl derivatives of dihydrotetrabenazine as positron emission tomography imaging agents targeting vesicular monoamine transporters. Nucl Med Biol. 2006 Aug;33(6):685-94. doi: 10.1016/j.nucmedbio.2006.05.006. | |
| 17383572 | Background | Kilbourn MR, Hockley B, Lee L, Hou C, Goswami R, Ponde DE, Kung MP, Kung HF. Pharmacokinetics of [(18)F]fluoroalkyl derivatives of dihydrotetrabenazine in rat and monkey brain. Nucl Med Biol. 2007 Apr;34(3):233-7. doi: 10.1016/j.nucmedbio.2007.01.007. |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C549477 | florbenazine F 18 |
| D001120 | Arginine |
| ID | Term |
|---|---|
| D024361 | Amino Acids, Basic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000599 | Amino Acids, Diamino |
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Blood plasma
| Arginine-hydrochloride | Biological | A bolus injection of 5g of 10% arginine-hydrochloride will be given over a period of 1 minute. |
|
| 17383573 | Background | Kung MP, Hou C, Goswami R, Ponde DE, Kilbourn MR, Kung HF. Characterization of optically resolved 9-fluoropropyl-dihydrotetrabenazine as a potential PET imaging agent targeting vesicular monoamine transporters. Nucl Med Biol. 2007 Apr;34(3):239-46. doi: 10.1016/j.nucmedbio.2006.12.005. |
| 18552132 | Background | Kung MP, Hou C, Lieberman BP, Oya S, Ponde DE, Blankemeyer E, Skovronsky D, Kilbourn MR, Kung HF. In vivo imaging of beta-cell mass in rats using 18F-FP-(+)-DTBZ: a potential PET ligand for studying diabetes mellitus. J Nucl Med. 2008 Jul;49(7):1171-6. doi: 10.2967/jnumed.108.051680. Epub 2008 Jun 13. |
| 9686917 | Background | Larsson H, Ahren B. Glucose-dependent arginine stimulation test for characterization of islet function: studies on reproducibility and priming effect of arginine. Diabetologia. 1998 Jul;41(7):772-7. doi: 10.1007/s001250050986. |
| 18049122 | Background | Rickels MR, Naji A, Teff KL. Acute insulin responses to glucose and arginine as predictors of beta-cell secretory capacity in human islet transplantation. Transplantation. 2007 Nov 27;84(10):1357-60. doi: 10.1097/01.tp.0000287595.16442.a7. |
| 16710474 | Background | Souza F, Simpson N, Raffo A, Saxena C, Maffei A, Hardy M, Kilbourn M, Goland R, Leibel R, Mann JJ, Van Heertum R, Harris PE. Longitudinal noninvasive PET-based beta cell mass estimates in a spontaneous diabetes rat model. J Clin Invest. 2006 Jun;116(6):1506-13. doi: 10.1172/JCI27645. Epub 2006 May 18. |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D000601 | Amino Acids, Essential |