Abstract
OBJECTIVES: The exact cause(s) of apparent overestimation of β cell mass (BCM) with vesicular monoamine transporter type 2 (VMAT2) PET imaging in type 1 diabetes (T1D) is unknown. The objectives were to estimate in baboons non-displaceable binding of [¹⁸F]fluoropropyl (FP)-(+)-dihydrotetrabenazine (DTBZ) with its inactive enantiomer, [¹⁸F]FP-(-)-DTBZ, to validate the use of the reference tissue (renal cortex or spleen) in VMAT2 quantification; and also to compare specific pancreatic VMAT2 binding with that of the striatum in the same baboon brains because high specific binding signal for the pancreas would be desirable for its accurate quantification. METHODS: Baboons (Papio ursinus) had multiple dynamic abdominal and brain PET scans each for 2 h with (+) and (-) enantiomers on separate occasions. Data were analyzed by compartmental models to estimate non-displaceable (V(ND)) and specific (V(S)) VMAT2 binding in respective organs. RESULTS: [¹⁸F]FP-DTBZ PET showed excellent target tissue signal and specific VMAT2 binding in the pancreas (Vs =41±11 mL/cm³) at nearly 80% that of the striatum. Directly estimated non-displaceable binding in the pancreas (V(ND) =12±1 mL/cm³) was similar to that of the renal cortex, spleen or cerebellum. CONCLUSION: ¹⁸FFP-DTBZ PET shows excellent specific VMAT2 binding in both the pancreas and striatum in baboons. The renal cortex or spleen as the reference tissue in VMAT2 quantification appears supported. However further studies appear warranted to directly estimate pancreatic non-displaceable binding in humans including T1D patients and also to clarify the cause of the apparent overestimation of BCM in T1D.