Test–retest reproducibility of the metabotropic glutamate receptor 5 ligand [18F]FPEB with bolus plus constant infusion in humans

Abstract

Purpose: [18F]FPEB is a promising PET radioligand for the metabotropic glutamate receptor 5 (mGluR5), a potential target for the treatment of neuropsychiatric diseases. The purpose of this study was to evaluate the test–retest reproducibility of [18F]FPEB in the human brain. Methods: Seven healthy male subjects were scanned twice, 3 – 11 weeks apart. Dynamic data were acquired using bolus plus infusion of 162 ± 32 MBq [18F]FPEB. Four methods were used to estimate volume of distribution (VT): equilibrium analysis (EQ) using arterial (EQA) or venous input data (EQV), MA1, and a two-tissue compartment model (2 T). Binding potential (BPND) was also estimated using cerebellar white matter (CWM) or gray matter (CGM) as the reference region using EQ, 2 T and MA1. Absolute test–retest variability (aTRV) of VT and BPND were calculated for each method. Venous blood measurements (CV) were compared with arterial input (CA) to examine their usability in EQ analysis. Results: Regional VT estimated by the four methods displayed a high degree of agreement (r2 ranging from 0.83 to 0.99 among the methods), although EQA and EQV overestimated VT by a mean of 9 % and 7 %, respectively, compared to 2 T. Mean values of aTRV of VT were 11 % by EQA, 12 % by EQV, 14 % by MA1 and 14 % by 2 T. Regional BPND also agreed well among the methods and mean aTRV of BPND was 8 – 12 % (CWM) and 7 – 9 % (CGM). Venous and arterial blood concentrations of [18F]FPEB were well matched during equilibrium (CV = 1.01 · CA, r2 = 0.95). Conclusion: [18F]FPEB binding shows good TRV with minor differences among analysis methods. Venous blood can be used as an alternative for input function measurement instead of arterial blood in EQ analysis. Thus, [18F]FPEB is an excellent PET imaging tracer for mGluR5 in humans.