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 two-tissue compartment model (2T). Binding potential (BPND) was also estimated using cerebellar white matter (CWM) or grey matter (CGM) as a reference region using EQ, 2T 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 for EQ analysis. Results Regional VT estimated by the four methods displayed a high degree of agreement (r2 ranging from 0.83 to 0.99 between methods), although EQA and EQV overestimated VT by a mean of 9% and 7%, respectively, compared to 2T. Mean aTRV of VT were 11% by EQA, 12% by EQV, 14% by MA1 and 14% by 2T. Regional BPND also agreed well between 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 test-retest variability with minor differences between 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.

Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence

“…Based on previous studies showing that equilibrium was reached at 60 min, emission data were acquired 90-120 min after the start of injection on the high-resolution research tomograph (Siemens/CTI), which has intrinsic spatial resolution of ∼2.5 mm FWHM. We have previously shown that venous and arterial concentrations are wellmatched at equilibrium, allowing venous sampling to be collected for metabolite correction as opposed to the more invasive arterial sampling (19). We also showed good test-retest variability (mean TRV of 12%) of […”

“…[ 18 F]FPEB was administered i.v. as bolus plus infusion for 120 min, with a K bol of 190 min (19,76). Based on previous studies showing that equilibrium was reached at 60 min, emission data were acquired 90-120 min after the start of injection on the high-resolution research tomograph (Siemens/CTI), which has intrinsic spatial resolution of ∼2.5 mm FWHM.…”

“…18 F]FPEB binding using this approach (19). Venous samples were acquired at 15,20,25,30,40,50,60,75,90,105, and 120 min postinjection for calculation of a metabolite-corrected venous input function as validated previously (19).…”

“…T1-weighted MRI scans were acquired on a 3T scanner (Trio; Siemens Medical Systems) to exclude structural abnormality and for coregistration with PET. [ 18 F]FPEB was synthesized onsite as described previously (19). [ 18 F]FPEB was administered i.v.…”

“…In study 1, we used PET and [ 18 F]FPEB, a radioligand that binds to the negative allosteric modulator site on mGluR5 with high selectivity and specificity (19,20), to quantify mGluR5 availability in individuals with PTSD. We hypothesized that cortical mGluR5 availability would be altered in PTSD, with the largest alterations in individuals with the most severe PTSD symptoms.…”