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

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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. βtar and βref 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 SUVR50-80 min, SUVRc50-80 min, SUVR15-45 min and DVR. SUVR50-80 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 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 min was 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 min reduced bias compared to SUVR50-80 min, as previously reported. SUVRc50-80 min was 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.

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