Early peak equilibrium is superior to late pseudo-equilibrium for simplified quantification of ¹⁸F-FE-PE2I PET

Introduction: Imaging the presynaptic dopamine transporter (DAT) is important for the differential diagnosis of parkinsonism and provides a potential progression marker for Parkinson`s disease (PD). The PET-radioligand ¹⁸F-FE-PE2I enables precise quantification of DAT availability, though the optimal time window for shortened acquisition protocols is still under debate. This study examines cross-sectional, test-retest, and longitudinal ¹⁸F-FE-PE2I PET data to assess the reliability of simplified binding ratios (SBR) derived from image frames during early peak and late pseudo-equilibrium.

Methods: We enrolled 33 PD patients (63±9y) and 24 healthy controls (62±8y). The participants performed a 93 minute dynamic ¹⁸F-FE-PE2I PET scan. Two subgroups of patients had a second examination after either 12±7d (test-retest: 10 PD patients, 63±9y) or 2±0y (longitudinal: 12 PD patients, 62±8y). All PET measurements were used to calculate SBR for MRI-based volumes of interest of the caudate nucleus and the putamen on summarized images during the early (15-45 min) and late (50-80 min) equilibrium using the cerebellum as reference region. The binding potential (BP_ND) according to the simplified reference tissue model served as gold standard. Receiver operator characteristics (ROC) analysis (PD vs. controls) was performed to calculate the area under the curve (AUC) for putamen SBR. In the cross-sectional cohort, Cohen´s d and coefficient of variation [CV] were measures of effect size and variability. In the test-retest cohort intraclass correlation coefficient [ICC] and absolute percentage difference [APD] were measures of agreement. Annual percentage change (APC) of SBR was calculated for the longitudinal cohort.

Results: The ROC AUC was high for early and late SBR (0.996/0.990). The metrics of early SBR were more favourable and closer to the reference standard than late SBR in both caudate (d: 1.26 vs. 1.16; CV: 0.36 vs. 0.47; ICC: 0.95 vs. 0.90; mean APD: 8.0% vs. 14.0%) and putamen (d: 1.75 vs. 1.65; CV: 0.57 vs. 0.75; ICC: 0.90 vs. 0.80; mean APD: 8.8% vs. 17.8%). Mean APC was comparable for early and late SBR in the caudate (-7.3%/-7.5%) and in the putamen (-7.4/-8.5%). Conclusion: A 30 minute ¹⁸F-FE-PE2I PET acquisition during either early peak or late pseudo-equilibrium retains discriminative power to separate PD patients and healthy controls. However, the better test-retest reliability of the early peak equilibrium indicates that this acquisition is preferable if ¹⁸F-FE-PE2I is used as marker for disease severity and progression. Acknowledgements: This work has been supported by the grants from Swedish Science Council, a private donation, Åhlen Foundation and by the Deutsche Forschungsgemeinschaft (DFG, BR 6121/1-1).