title: In vivo imaging of endogenous pancreatic β-cell mass in healthy and type 1 diabetic subjects using 18F-fluoropropyl-dihydrotetrabenazine and PET.
abstract: The ability to noninvasively measure endogenous pancreatic β-cell mass (BCM) would accelerate research on the pathophysiology of diabetes and revolutionize the preclinical development of new treatments, the clinical assessment of therapeutic efficacy, and the early diagnosis and subsequent monitoring of disease progression. The vesicular monoamine transporter type 2 (VMAT2) is coexpressed with insulin in β-cells and represents a promising target for BCM imaging.
  
  
  METHODS
  We evaluated the VMAT2 radiotracer (18)F-fluoropropyl-dihydrotetrabenazine ((18)F-FP-(+)-DTBZ, also known as (18)F-AV-133) for quantitative PET of BCM in healthy control subjects and patients with type 1 diabetes mellitus. Standardized uptake value was calculated as the net tracer uptake in the pancreas normalized by injected dose and body weight. Total volume of distribution, the equilibrium ratio of tracer concentration in tissue relative to plasma, was estimated by kinetic modeling with arterial input functions. Binding potential, the steady-state ratio of specific binding to nondisplaceable uptake, was calculated using the renal cortex as a reference tissue devoid of specific VMAT2 binding.
  
  
  RESULTS
  Mean pancreatic standardized uptake value, total volume of distribution, and binding potential were reduced by 38%, 20%, and 40%, respectively, in type 1 diabetes mellitus. The radiotracer binding parameters correlated with insulin secretion capacity as determined by arginine-stimulus tests. Group differences and correlations with β-cell function were enhanced for total pancreas binding parameters that accounted for tracer binding density and organ volume.
  
  
  CONCLUSIONS
  These findings demonstrate that quantitative evaluation of islet β-cell density and aggregate BCM can be performed clinically with (18)F-FP-(+)-DTBZ PET.
authors.affiliation: Department of Diagnostic Radiology, Yale University, School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Normandin
authors.forename: Kitt F
authors.initials: KF
authors.lastname: Petersen
authors.forename: Yu-Shin
authors.initials: YS
authors.lastname: Ding
authors.forename: Shu-Fei
authors.initials: SF
authors.lastname: Lin
authors.forename: Sarita
authors.initials: S
authors.lastname: Naik
authors.forename: Krista
authors.initials: K
authors.lastname: Fowles
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Skovronsky
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: McCarthy
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Calle
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.forename: Judith L
authors.initials: JL
authors.lastname: Treadway
authors.forename: Gary W
authors.initials: GW
authors.lastname: Cline
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000000981:diagnostic imaging*; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D050417:Insulin-Secreting Cells / Q000000981:diagnostic imaging* / Q000502:physiology; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D013747:Tetrabenazine / Q000031:analogs & derivatives*
chemical_list: D005462:Fluorine Radioisotopes; C549477:florbenazine F 18; D013747:Tetrabenazine