RGD Reference Report - 11C-dihydrotetrabenazine PET of the pancreas in subjects with long-standing type 1 diabetes and in healthy controls. - Rat Genome Database

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11C-dihydrotetrabenazine PET of the pancreas in subjects with long-standing type 1 diabetes and in healthy controls.

Authors: Goland, R  Freeby, M  Parsey, R  Saisho, Y  Kumar, D  Simpson, N  Hirsch, J  Prince, M  Maffei, A  Mann, JJ  Butler, PC  Van Heertum, R  Leibel, RL  Ichise, M  Harris, PE 
Citation: Goland R, etal., J Nucl Med. 2009 Mar;50(3):382-9. Epub 2009 Feb 17.
RGD ID: 5131199
Pubmed: PMID:19223416   (View Abstract at PubMed)
PMCID: PMC3629294   (View Article at PubMed Central)
DOI: DOI:10.2967/jnumed.108.054866   (Journal Full-text)

Type 2 vesicular monoamine transporter (VMAT2), found in the brain, is also expressed by beta-cells of the pancreas in association with insulin. Preclinical experiments suggested that (11)C-dihydrotetrabenazine PET-measured VMAT2 binding might serve as a biomarker of beta-cell mass. We evaluated the feasibility of (11)C-dihydrotetrabenazine PET quantification of pancreatic VMAT2 binding in healthy subjects and patients with long-standing type 1 diabetes. METHODS: (11)C-Dihydrotetrabenazine PET was performed on 6 patients and 9 controls. VMAT2 binding potential (BP(ND)) was estimated voxelwise by using the renal cortex as reference tissue. As an index of total pancreatic VMAT2, the functional binding capacity (the sum of voxel BP(ND) x voxel volume) was calculated. Pancreatic BP(ND), functional binding capacity, and stimulated insulin secretion measurements were compared between groups. RESULTS: The pancreatic mean BP(ND) was decreased in patients (1.86 +/- 0.05) to 86% of control values (2.14 +/- 0.08) (P = 0.01). In controls, but not in patients, BP(ND) correlated with stimulated insulin secretion (r(2) = 0.50, P = 0.03). The average functional binding capacity was decreased by at least 40% in patients (P = 0.001). The changes in functional binding capacity and BP(ND) were less than the near-complete loss of stimulated insulin secretion observed in patients (P = 0.001). CONCLUSION: These results suggest that (11)C-dihydrotetrabenazine PET allows quantification of VMAT2 binding in the human pancreas. However, BP(ND) and functional binding capacity appear to overestimate beta-cell mass given the near-complete depletion of beta-cell mass in long-standing type 1 diabetes, which may be due to higher nonspecific binding in the pancreas than in the renal cortex.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SLC18A2Humantype 1 diabetes mellitus  IEP protein:decreased expression:pancreas (human)RGD 
Slc18a2Rattype 1 diabetes mellitus  ISOSLC18A2 (Homo sapiens)protein:decreased expression:pancreas (human)RGD 
Slc18a2Mousetype 1 diabetes mellitus  ISOSLC18A2 (Homo sapiens)protein:decreased expression:pancreas (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc18a2  (solute carrier family 18 member A2)

Genes (Mus musculus)
Slc18a2  (solute carrier family 18 (vesicular monoamine), member 2)

Genes (Homo sapiens)
SLC18A2  (solute carrier family 18 member A2)


Additional Information