Optimal Acquisition Time Window and Simplified Quantification of Dopamine Transporter Availability Using 18F-FE-PE2I in Healthy Controls and Parkinson Disease Patients

¹⁸F-(E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β-(4'methylphenyl)nortropane (¹⁸F-FE-PE2I) is a newly developed dopamine transporter (DAT) PET radioligand. Full quantification methods rely on dynamic acquisition of ¹⁸F-FE-PE2I, but in a clinical setting a simplified protocol is preferable. The aims of this study were to identify the optimal acquisition time window for ¹⁸F-FE-PE2I and to validate the specific binding ratio (SBR) as a simplified quantification method.

Methods: Ten Parkinson disease (PD) patients and 10 controls were included. Ninety-three-min dynamic PET measurements with ¹⁸F-FE-PE2I were conducted using the high-resolution research tomograph (HRRT). The dynamic measurement was also smoothed to the resolution of a clinical PET system (HR). Regions of interest for the caudate, putamen, ventral striatum, substantia nigra (SN), and cerebellum were manually drawn on coregistered MR images. The outcome measure was the SBR, and the gold standard was the binding potential obtained with wavelet-aided parametric imaging (WAPI BP_ND). The cerebellum was used as a reference region. In a preliminary analysis, SBR was computed for 8 time windows (SBR_dyn). Linear regression analysis and Bland-Altman plots were used to select the optimal acquisition time window. An average image from the selected time window was created, from which new SBR values (SBR calculated on the average image on the HRRT and SBR calculated on the average image on the simulated HR images) were calculated and compared with WAPI BP_ND The effect size was calculated.

Results: SBR_dyn values for the time window between 16.5 and 42 min correlated best with WAPI BP_ND (r² = 0.98, P < 0.001). Significant correlations (P < 0.001) were observed between SBR_HR and WAPI-BP_ND (r² = 0.95 in controls and 0.97 in PD patients). In the striatum, SBR_HR values were 37% lower than BP_ND in controls, 29% in PD patients, whereas in the SN the underestimation was 22% in controls and 15% in PD patients. Similar effect sizes for BP_ND and SBR_HR were found in the caudate (0.6), putamen (1.7 and 1.4), ventral striatum (0.7), and SN (0.5 and 0.4).

Conclusion: A single ¹⁸F-FE-PE2I acquisition between 16.5 and 42 min provides the best outcome measure for simplified DAT quantification. Despite underestimation of the BP_ND, the SBR can be used in a clinical setting as a valid quantification method for DAT using ¹⁸F-FE-PE2I, because it provides differentiation similar to BP_ND between controls and PD patients.