Background This study aimed to quantify relative cerebral blood flow (rCBF, R1) and dopamine transporter (DAT) availability in subjects with Parkinson’s disease (PD) using positron emission tomography (PET) with [ 18 F]FE-PE2I. We investigated group differences in R1, test–retest variability (TRV), associations with DAT availability, and annual longitudinal changes (ALC). Results Cross-sectional (38 PD, 35 age- and gender-matched controls), test-retest (9 PD) and longitudinal (19 PD) cohorts were included. R1 and binding potential (BP ND ) values were estimated in the striatum (STR), substantia nigra (SN), and cortical regions. Group differences in R1 and associations with DAT availability were assessed cross-sectionally. In PD subjects, TRV and ALC over 2 years were calculated. PD subjects showed significantly lower R1 in STR (0.94 ± 0.08 vs. 1.05 ± 0.11, p < 0.001) and occipital cortex (0.99 ± 0.07 vs. 1.04 ± 0.07, p = 0.006) compared with controls. Low to moderate positive correlations was found between R1 and DAT availability in STR and SN of PD subjects (r 2 = 0.41 and 0.3, p < 0.001) and controls (r 2 = 0.28 and 0.42, p < 0.001). TRV was 5.06% in STR [range:4.06;6.82], 5.41% in SN [4.38;9.33] and ranged from 1.47% [0.85;3.72] to 2.80 [1.23;4.42] across cortical regions. ALC in the STR and SN were 1.95% [0.48;4.21] and − 0.47 [-2.42;4.60] and ranged from 0.92% [-0.37;1.35] to 1.17% [0.41;3.46] across cortical regions. Conclusions rCBF is reduced in the striatum and occipital cortex in PD, correlated positively with DAT availability and exhibited adequate test-retest reproducibility. Longitudinal changes of rCBF within 2-y interval were smaller than the TRV, suggesting relative stability of rCBF despite progressive DAT loss. Trial registration number The study was prospectively registered in the EudraCT database (EudraCT No. 2011-002005-30, registered on 26 April 2011; 2017-001585-19, registered on 2 August 2017; and 2017-003327-29, registered on 8 October 2017).
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