Cross-sectional and Test-Retest Characterization of PET with [(18)F]FP-(+)-DTBZ for β Cell Mass Estimates in Diabetes

Mol Imaging Biol. 2016 Apr;18(2):292-301. doi: 10.1007/s11307-015-0888-7. Epub 2015 Sep 14.

Abstract

Purpose: The vesicular monoamine transporter, type 2 (VMAT2) is expressed by insulin producing β cells and was evaluated as a biomarker of β cell mass (BCM) by positron emission tomography (PET) with [(18)F]fluoropropyl-dihydrotetrabenazine ([(18)F]FP-(+)-DTBZ).

Procedures: We evaluated the feasibility of longitudinal pancreatic PET VMAT2 quantification in the pancreas in two studies of healthy controls and patients with type 1 or 2 diabetes. VMAT2 binding potential (BPND) was estimated voxelwise using a reference tissue method in a cross-sectional study, followed by assessment of reproducibility using a test-retest paradigm. Metabolic function was evaluated by stimulated c-peptide measurements.

Results: Pancreatic BPND was significantly decreased in patients with type 1 diabetes relative to controls and the test-retest variability was 9.4%.

Conclusions: Pancreatic VMAT2 content is significantly reduced in long-term diabetes patients relative to controls and repeat scans are sufficiently reproducible to suggest the feasibility clinically VMAT2 measurements in longitudinal studies of new onset diabetes.

Keywords: Beta cell mass; Diabetes; PET; Test-retest; VMAT2; [18F]FP-(+)-DTBZ.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Case-Control Studies
  • Cell Size
  • Demography
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Fluorine Radioisotopes / metabolism*
  • Glucose / pharmacology
  • Humans
  • Insulin / genetics
  • Insulin / metabolism
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology*
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods*
  • Protein Binding / drug effects
  • Tetrabenazine / analogs & derivatives*
  • Tetrabenazine / metabolism
  • Vesicular Monoamine Transport Proteins / genetics
  • Vesicular Monoamine Transport Proteins / metabolism

Substances

  • Fluorine Radioisotopes
  • Insulin
  • SLC18A2 protein, human
  • Vesicular Monoamine Transport Proteins
  • Glucose
  • florbenazine F 18
  • Tetrabenazine