Abstract
95
Objectives Vesicular monoamine transporter type 2 (VMAT2), imaged with 18F-FP-(+)-DTBZ, is a promising biomarker of insulin-secreting pancreatic β-cell mass. In an ex vivo study in baboons with 18F-FP-(+)-DTBZ and its weak affinity (Ki>3000 nM) enantiomer, 18F-FP-(-)-DTBZ, metabolite uptake in organs was heterogeneous. We examined binding kinetics of 18F-FP-(+)-DTBZ and 18F-FP-(-)-DTBZ to estimate the specific and non-specific binding of the tracer in the pancreas in baboons and humans. We also assessed the binding profiles of the two tracers following displacement with cold (-)- or (+)-FPDTBZ, or fluvoxamine (to assess sigma receptor binding).
Methods Four baboons were scanned on the HR+ scanner. For both tracers, a control scan and displacement scans with either cold (-)-FPDTBZ (0.5 mg/kg), (+)-FPDTBZ (0.25 or 0.5 mg/kg), or fluvoxamine (3 mg/kg) were performed. Regional time-activity curves were generated for pancreas, renal cortex, and spleen on summed PET images. The % reduction in the pancreas SUV was calculated. Two healthy human subjects were also scanned with both tracers on the mCT scanner. Distribution volumes (VT) were estimated for all control scans.
Results VT in baboons and humans was summarized in the Table. Regional rank order of VT was different between species and between tracers. Displacement with cold (-)-FPDTBZ led to little change in SUV of either 18F-FP-(-)-DTBZ (-1%) or 18F-FP-(+)-DTBZ (7%). In contrast, cold (+)-FPDTBZ induced significant decrease in 18F-FP-(+)-DTBZ binding (24-48%), but had little effect on 18F-FP-(-)-DTBZ (14%). Fluvoxamine had negligible effect on 18F-FP-(+)-DTBZ binding (6-7%).
Conclusions Based on VT values, up to 85% of pancreatic uptake of 18F-FP-(+)-DTBZ is VMAT2 specific binding, while 18F-FP-(-)-DTBZ specific binding is negligible. Different rank order of uptake in baboons and humans for the two isomers might be due to differences in metabolite uptake among organs.
Research Support JDRF 37-2011-633