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

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 (<i>SUVR</i>c) for a less-biased estimate of <i>SUVR</i> 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). <i>SUVR</i>c was calculated as <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mfrac><mml:mrow><mml:mi>SUVR</mml:mi></mml:mrow><mml:mrow><mml:mn>1</mml:mn><mml:mi> </mml:mi><mml:mo>-</mml:mo><mml:mi> </mml:mi><mml:mfrac><mml:mrow><mml:msub><mml:mrow><mml:mi>β</mml:mi></mml:mrow><mml:mrow><mml:mi>ref</mml:mi></mml:mrow></mml:msub></mml:mrow><mml:mrow><mml:msub><mml:mrow><mml:mi>k</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn><mml:mo>,</mml:mo><mml:mi>ref</mml:mi></mml:mrow></mml:msub></mml:mrow></mml:mfrac><mml:mi> </mml:mi><mml:mo>+</mml:mo><mml:msub><mml:mrow><mml:mi>β</mml:mi></mml:mrow><mml:mrow><mml:mi>tar</mml:mi></mml:mrow></mml:msub><mml:mfrac><mml:mrow><mml:mi>SUVR</mml:mi></mml:mrow><mml:mrow><mml:msub><mml:mrow><mml:mi>k</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn><mml:mo>,</mml:mo><mml:mi>ref</mml:mi></mml:mrow></mml:msub><mml:msub><mml:mrow><mml:mi>R</mml:mi></mml:mrow><mml:mrow><mml:mn>1</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:mfrac></mml:mrow></mml:mfrac></mml:math>. <i>β</i>_tar and <i>β</i>_ref are the clearance rates from the target and reference tissues. Bias relative to <i>DVR</i>, discriminative power, test-retest variability (TRV) and annual longitudinal change (ALC) were used to compare <i>SUVR</i>_{50-80 min}, <i>SUVR</i>c_{50-80 min}, <i>SUVR</i>_{15-45 min} and <i>DVR. SUVR</i>_{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 <i>SUVR</i>c_{50-80 min} (HC: -0.80 ± 12.72% [-9.69-11.64%]; PD: -0.13 ± 7.41% [-5.04-2.97%]), <i>p < </i>0.001 for both groups compared to mean bias of <i>SUVR</i>_{50-80 min}, similar to <i>SUVR</i>_{15-45 min}. For the striatum, Cohen's <i>d</i> was similar for all measures. TRV were 3.2 ± 2.5% (<i>DVR</i>), 6.4 ± 5.7% (<i>SUVR</i>_{50-80 min}), 6.8 ± 5.9% (<i>SUVR</i>c_{50-80 min}) and 3.9 ± 3.2% (<i>SUVR</i>_{15-45 min}). Higher TRV of <i>SUVR</i>c_{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% (<i>DVR</i>), 5.2 ± 6.5% (<i>SUVR</i>_{50-80 min}), 4.4 ± 4.1% (<i>SUVR</i>c_{50-80 min}) and 4.2 ± 4.1% (<i>SUVR</i>_{15-45 min}). <i>SUVR</i>c_{50-80 min} reduced bias compared to <i>SUVR</i>_{50-80 min}, as previously reported. <i>SUVR</i>c_{50-80 min} was sensitive to small changes of β_tar, with higher TRV compared to <i>DVR</i>, but with similar ALC, suggesting that it can reliably assess longitudinal DAT changes.