Abstract
INTRODUCTION: (18)F-Fluoropropyl-(+)-dihydrotetrabenazine ((18)F-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 (18)F-FP-(+)-DTBZ binding in these regions including the fraction of radiometabolite. We compared the kinetics of (18)F-FP-(+)-DTBZ and its inactive enantiomer (18)F-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 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 (V(T)) were computed, and three approaches for calculation of V(ND) were compared: (1) (18)F-FP-(+)-DTBZ reference V(T), (2) (18)F-FP-(-)-DTBZ pancreatic V(T), and (3) a scaled (18)F-FP-(+)-DTBZ reference V(T) 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 (18)F-FP-(+)-DTBZ and renal cortex with (18)F-FP-(-)-DTBZ. Substantial displacement effect was observed only with unlabeled FP-(+)-DTBZ in the (18)F-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 (18)F-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 (18)F-FP-(+)-DTBZ in the pancreas.