Correcting SUVR bias by accounting for radiotracer clearance in tissue: A validation study with [18F]FE-PE2I PET in cross-sectional, test-retest and longitudinal cohorts

Abstract

Quantification of dopamine transporter (DAT) with [18F]FE-PE2I PET is an important progression marker for Parkinson’s disease (PD). This study aimed to validate a novel correction (SUVRc) for a less-biased estimate of SUVR by accounting for [18F]FE-PE2I clearance-rate, in independent cross-sectional (38 PD, 38 controls), test-retest (9 PD) and longitudinal cohorts (21 PD). SUVRc was calculated as SUVR1 − βrefk2,ref +βtarSUVRk2,refR1[jls-end-space/]. βtarand βrefare the clearance rates from the target and reference tissues. Bias relative to DVR, discriminative power, test-retest variability (TRV) and annual longitudinal change (ALC) were used to compare SUVR50–80 min, SUVRc50–80 min, SUVR15–45 minand DVR. SUVR50–80 minshowed high bias across all regions (HC: mean: 48.31 ± 20.49% [range: 28.32–53.80%]; PD: 29.91 ± 13.95% [20.45–39.80%]) that was corrected by SUVRc50–80 min(HC: −0.80 ± 12.72% [−9.69–11.64%]; PD: −0.13 ± 7.41% [−5.04–2.97%]), p < 0.001 for both groups compared to mean bias of SUVR50–80 min, similar to SUVR15–45 min. For the striatum, Cohen’s d was similar for all measures. TRV were 3.2 ± 2.5% (DVR), 6.4 ± 5.7% (SUVR50–80 min), 6.8 ± 5.9% (SUVRc50–80 min) and 3.9 ± 3.2% (SUVR15–45 min). Higher TRV of SUVRc50–80 minwas due to TRV of 9.2 ± 5.1% [1.1–19.4] for βtar. ALC was 4.5 ± 4.2% (DVR), 5.2 ± 6.5% (SUVR50–80 min), 4.4 ± 4.1% (SUVRc50–80 min) and 4.2 ± 4.1% (SUVR15–45 min). SUVRc50–80 minreduced bias compared to SUVR50–80 min, as previously reported. SUVRc50–80 minwas sensitive to small changes of βtar, with higher TRV compared to DVR, but with similar ALC, suggesting that it can reliably assess longitudinal DAT changes.