Evaluation of Pancreatic VMAT2 Binding with Active and Inactive Enantiomers of [ 18 F]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 (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 [18 F]FP-(+)-DTBZ reference VT as VND , assuming VND is uniform across organs; (2) use of [18 F]FP-(-)-DTBZ pancreatic VT as VND , assuming that VND is uniform between enantiomers in the pancreas; and (3) use of a scaled [18 F]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: [18 F]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.