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 $\frac{\mathrm{SUVR}}{1 - \frac{{\beta }_{\mathrm{ref}}}{k_{2,\mathrm{ref}}} +{\beta }_{\mathrm{tar}}\frac{\mathrm{SUVR}}{k_{2,\mathrm{ref}}{R}_1}}$. β_tar and β_ref are 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 SUVR_50-80 min, SUVRc_50-80 min, SUVR_15-45 min and DVR. SUVR_50-80 min showed 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 SUVRc_50-80 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 SUVR_50-80 min, similar to SUVR_15-45 min. For the striatum, Cohen's d was similar for all measures. TRV were 3.2 ± 2.5% (DVR), 6.4 ± 5.7% (SUVR_50-80 min), 6.8 ± 5.9% (SUVRc_50-80 min) and 3.9 ± 3.2% (SUVR_15-45 min). Higher TRV of SUVRc_50-80 min was due to TRV of 9.2 ± 5.1% [1.1-19.4] for β_tar. ALC was 4.5 ± 4.2% (DVR), 5.2 ± 6.5% (SUVR_50-80 min), 4.4 ± 4.1% (SUVRc_50-80 min) and 4.2 ± 4.1% (SUVR_15-45 min). SUVRc_50-80 min reduced bias compared to SUVR_50-80 min, as previously reported. SUVRc_50-80 min was sensitive to small changes of β_tar, with higher TRV compared to DVR, but with similar ALC, suggesting that it can reliably assess longitudinal DAT changes.