Evaluation of Pancreatic VMAT2 Binding with Active and Inactive Enantiomers of [18F]FP-DTBZ in Healthy Subjects and Patients with Type 1 Diabetes.

Purpose: Previous studies demonstrated the utility of [18F]fluoropropyl-(+)-dihydrotetrabenazine ([18F]FP-(+)-DTBZ) as a positron emission tomography (PET) radiotracer for the vesicular monoamine transporter type 2 (VMAT2) to quantify beta cell mass in healthy control (HC) and type 1 diabetes mellit...

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Publicado en:Molecular Imaging & Biology Vol. 20; no. 5; pp. 835 - 846
Autores principales: Naganawa, Mika, Lim, Keunpoong, Nabulsi, Nabeel B., Lin, Shu-fei, Labaree, David, Ropchan, Jim, Herold, Kevan C., Huang, Yiyun, Harris, Paul, Ichise, Masanori, Cline, Gary W., Carson, Richard E.
Formato: research Journal Article
Publicado: Springer Nature Oct2018
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Oct2018
      vid: 20
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s11307-018-1170-6
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        atl: Evaluation of Pancreatic VMAT2 Binding with Active and Inactive Enantiomers of [18F]FP-DTBZ in Healthy Subjects and Patients with Type 1 Diabetes.
      aug:
        au:
          Naganawa, Mika
          Lim, Keunpoong
          Nabulsi, Nabeel B.
          Lin, Shu-fei
          Labaree, David
          Ropchan, Jim
          Herold, Kevan C.
          Huang, Yiyun
          Harris, Paul
          Ichise, Masanori
          Cline, Gary W.
          Carson, Richard E.
        affil: Yale University, P.O. Box 208048, 06520-8048, New Haven, CT, USA
      sug:
        subj:
          Heterocyclic Compounds Analogs and Derivatives
          Diabetes Mellitus, Type 1 Metabolism
          Diabetes Mellitus, Type 1
          Fluorine Radioisotopes Blood
          Young Adult
          Heterocyclic Compounds Pharmacokinetics
          Fluorine Radioisotopes
          Diabetes Mellitus, Type 1 Blood
          Case Control Studies
          Adult
          Heterocyclic Compounds Blood
          Human
          Male
          Chemistry
          Female
          Heterocyclic Compounds
          Fluorine Radioisotopes Pharmacokinetics
          Injections
          Validation Studies
          Comparative Studies
          Evaluation Research
          Multicenter Studies
          Adult: 19-44 years
          Male
          Female
      ab: Purpose: Previous studies demonstrated the utility of [18F]fluoropropyl-(+)-dihydrotetrabenazine ([18F]FP-(+)-DTBZ) as a positron emission tomography (PET) radiotracer for the vesicular monoamine transporter type 2 (VMAT2) to quantify beta cell mass in healthy control (HC) and type 1 diabetes mellitus (T1DM) groups. Quantification of specific binding requires measurement of non-displaceable uptake. Our goal was to identify a reference tissue (renal cortex or spleen) to quantify pancreatic non-specific binding of [18F]FP-(+)-DTBZ with the inactive enantiomer, [18F]FP-(-)-DTBZ. This was the first human study of [18F]FP-(-)-DTBZ.Procedures: Six HCs and four T1DM patients were scanned on separate days after injection of [18F]FP-(+)-DTBZ or [18F]FP-(-)-DTBZ. Distribution volumes (VT) and standardized uptake values (SUVs) were compared between groups. Three methods for calculation of non-displaceable uptake (VND) or reference SUV were applied: (1) use of [18F]FP-(+)-DTBZ reference VT as VND, assuming VND is uniform across organs; (2) use of [18F]FP-(-)-DTBZ pancreatic VT as VND, assuming that VND is uniform between enantiomers in the pancreas; and (3) use of a scaled [18F]FP-(+)-DTBZ reference VT as VND, assuming that a ratio of non-displaceable uptake between organs is uniform between enantiomers. Group differences in VT (or SUV), binding potential (BPND), or SUV ratio (SUVR) were estimated using these three methods.Results: [18F]FP-(-)-DTBZ VT values were different among organs, and VT(+) and VT(-) were also different in the renal cortex and spleen. Method 3 with the spleen to estimate VND (or reference SUV) gave the highest non-displaceable uptake and the largest HC vs. T1DM group differences. Significant group differences were also observed in VT (or SUV) with method 1 using spleen. SUV was affected by differences in the input function between groups and between enantiomers.Conclusions: Non-displaceable uptake was different among organs and between enantiomers. Use of scaled spleen VT values for VND is a suitable method for quantification of VMAT2 in the pancreas.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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