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 [ 18 F]fluoropropyl-(+)-dihydrotetrabenazine ([ 18 F]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 [ 18 F]FP-(+)-DTBZ with the inactive enantiomer, [ 18 F]FP-(−)-DTBZ. This was the first human study of [ 18 F]FP-(−)-DTBZ. Procedures Six HCs and four T1DM patients were scanned on separate days after injection of [ 18 F]FP-(+)-DTBZ or [ 18 F]FP-(−)-DTBZ. Distribution volumes ( V T ) and standardized uptake values (SUVs) were compared between groups. Three methods for calculation of non-displaceable uptake ( V ND ) or reference SUV were applied: (1) use of [ 18 F]FP-(+)-DTBZ reference V T as V ND , assuming V ND is uniform across organs; (2) use of [ 18 F]FP-(−)-DTBZ pancreatic V T as V ND , assuming that V ND is uniform between enantiomers in the pancreas; and (3) use of a scaled [ 18 F]FP-(+)-DTBZ reference V T as V ND , assuming that a ratio of non-displaceable uptake between organs is uniform between enantiomers. Group differences in V T (or SUV), binding potential ( BP ND ), or SUV ratio (SUVR) were estimated using these three methods. Results [ 18 F]FP-(−)-DTBZ V T values were different among organs, and V T (+) and V T (−) were also different in the renal cortex and spleen. Method 3 with the spleen to estimate V ND (or reference SUV) gave the highest non-displaceable uptake and the largest HC vs. T1DM group differences. Significant group differences were also observed in V T (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 V T values for V ND is a suitable method for quantification of VMAT2 in the pancreas.