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Nucl Med Biol. 2016 Dec;43(12):743-751. doi: 10.1016/j.nucmedbio.2016.08.018. Epub 2016 Sep 2.

Evaluation of pancreatic VMAT2 binding with active and inactive enantiomers of 18F-FP-DTBZ in baboons.

Author information

  • 1Yale University, 801 Howard Avenue, PO Box 208048, New Haven, CT, United States, 06520. Electronic address: mika.naganawa@yale.edu.
  • 2Yale University, 801 Howard Avenue, PO Box 208048, New Haven, CT, United States, 06520.
  • 3Columbia University, New York, NY, United States.

Abstract

INTRODUCTION:

18F-Fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-(+)-DTBZ) is a vesicular monoamine transporter type 2 (VMAT2) radiotracer for positron emission tomography (PET) imaging to quantify human β-cell mass. Renal cortex and spleen have been suggested as reference regions, however, little is known about 18F-FP-(+)-DTBZ binding in these regions including the fraction of radiometabolite. We compared the kinetics of 18F-FP-(+)-DTBZ and its inactive enantiomer 18F-FP-(-)-DTBZ in baboons, estimated the non-displaceable binding (VND) of the tracers, and used ex vivo studies to measure radiometabolite fractions.

METHODS:

PET scans were conducted for up to 4h with (+) and (-) enantiomers. Displacement experiments using unlabeled (+) and (-) enantiomers of FP-DTBZ and fluvoxamine (to evaluate sigma-1 receptor binding) were performed. SUV curves were used to calculate displacement values in the pancreas, renal cortex, and spleen. Distribution volumes (VT) were computed, and three approaches for calculation of VND were compared: (1) 18F-FP-(+)-DTBZ reference VT, (2) 18F-FP-(-)-DTBZ pancreatic VT, and (3) a scaled 18F-FP-(+)-DTBZ reference VT values. Ex vivo study was conducted to measure radiometabolite fraction in homogenized tissue samples from baboons at 90min post-injection.

RESULTS:

Spleen uptake was lowest for both tracers. Highest uptake was in the pancreas with 18F-FP-(+)-DTBZ and renal cortex with 18F-FP-(-)-DTBZ. Substantial displacement effect was observed only with unlabeled FP-(+)-DTBZ in the 18F-FP-(+)-DTBZ studies. Radiometabolite fraction was higher in the renal cortex than the spleen. Approaches (1) and (3) with spleen to estimate VND provided lowest inter-subject variability of BPND.

CONCLUSIONS:

VT differences among organs and between enantiomers indicated that scaling of reference region values is needed for quantification of VMAT2 binding in the pancreas with 18F-FP-(+)-DTBZ. Since the kidney PET signal has greater partial volume averaging and more radiometabolites, the spleen was considered a more practical candidate for use as a scaled-reference region in the quantification of 18F-FP-(+)-DTBZ in the pancreas.

KEYWORDS:

(18)F-FP-(+)-DTBZ; (18)F-FP-(−)-DTBZ; PET; Pancreas non-displaceable binding; Vesicular monoamine transporter type 2; β-cell mass

PMID:
27673755
PMCID:
PMC5248981
DOI:
10.1016/j.nucmedbio.2016.08.018
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