[en] 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 (V_ND) of the tracers, and used ex vivo studies to measure radiometabolite fractions. Methods: PET scans were conducted for up to 4 h 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 (V_T) were computed, and three approaches for calculation of V_ND were compared: (1) ¹⁸F-FP-(+)-DTBZ reference V_T, (2) ¹⁸F-FP-(−)-DTBZ pancreatic V_T, and (3) a scaled ¹⁸F-FP-(+)-DTBZ reference V_T values. Ex vivo study was conducted to measure radiometabolite fraction in homogenized tissue samples from baboons at 90 min 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 V_ND provided lowest inter-subject variability of BP_ND. Conclusions: V_T 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.