Evaluation of Pancreatic VMAT2 Binding with Active and Inactive Enantiomers of [F]FP-DTBZ in Healthy Subjects and Patients with Type 1 Diabetes.

PURPOSE

Previous studies demonstrated the utility of [F]fluoropropyl-(+)-dihydrotetrabenazine ([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 [F]FP-(+)-DTBZ with the inactive enantiomer, [F]FP-(-)-DTBZ. This was the first human study of [F]FP-(-)-DTBZ.

PROCEDURES

Six HCs and four T1DM patients were scanned on separate days after injection of [F]FP-(+)-DTBZ or [F]FP-(-)-DTBZ. Distribution volumes (V) and standardized uptake values (SUVs) were compared between groups. Three methods for calculation of non-displaceable uptake (V) or reference SUV were applied: (1) use of [F]FP-(+)-DTBZ reference V as V, assuming V is uniform across organs; (2) use of [F]FP-(-)-DTBZ pancreatic V as V, assuming that V is uniform between enantiomers in the pancreas; and (3) use of a scaled [F]FP-(+)-DTBZ reference V as V, assuming that a ratio of non-displaceable uptake between organs is uniform between enantiomers. Group differences in V (or SUV), binding potential (BP), or SUV ratio (SUVR) were estimated using these three methods.

RESULTS

[F]FP-(-)-DTBZ V values were different among organs, and V(+) and V(-) were also different in the renal cortex and spleen. Method 3 with the spleen to estimate V (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 (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 values for V is a suitable method for quantification of VMAT2 in the pancreas.