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 [¹⁸F]fluoropropyl-(+)-dihydrotetrabenazine ([¹⁸F]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 [¹⁸F]FP-(+)-DTBZ with the inactive enantiomer, [¹⁸F]FP-(-)-DTBZ. This was the first human study of [¹⁸F]FP-(-)-DTBZ.

Procedures: Six HCs and four T1DM patients were scanned on separate days after injection of [¹⁸F]FP-(+)-DTBZ or [¹⁸F]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 [¹⁸F]FP-(+)-DTBZ reference V_T as V_ND, assuming V_ND is uniform across organs; (2) use of [¹⁸F]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 [¹⁸F]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: [¹⁸F]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.