Alterations in regional cerebral perfusion in drug-induced Parkinsonism: Spatial covariance analyses of early-phase 18F-FP-CIT PET data.

BACKGROUND AND OBJECTIVES: Drug-induced Parkinsonism (DIP) develops in patients who are treated with drugs with D2 receptor-blocking activity, despite normal ranges of the striatal dopamine transporter (DAT) availability. This study aimed to investigate distinct cerebral perfusion patterns on early-phase 18F-FP-CIT PET in patients with DIP. METHODS: This retrospective study included 70 patients with DIP who showed visually preserved DAT availability in late-phase 18F-FP-CIT PET scans, 140 propensity score-matched patients with Parkinson's disease (PD), and 50 healthy controls. We used dual-phase 18F-FP-CIT PET to quantify striatal DAT availability (late-phase) and regional perfusion (early-phase), including DIP-related pattern (DIPRP) as well as PD-related pattern (PDRP) expression. Group differences were tested with ANCOVA adjusted for age and sex with false discovery rate correction. RESULTS: Compared with healthy controls, patients with DIP showed largely preserved striatal DAT availability and hypoperfusion in the frontal, insula, precuneus, occipital, limbic, and posterior cingulate cortices. Compared with PD, DIP exhibited greater frontal, insula, parietal, limbic, and posterior cingulate hypoperfusion but comparable occipital perfusion. The DIPRP and PDRP showed distinct spatial covariance topographies, while the DIPRP was characterized by prominent positive weights in the striatum and negative weights in distributed cortical regions. The severity of parkinsonian motor deficits correlated with DIPRP expression, but not with putaminal DAT availability, in patients with DIP. CONCLUSIONS: DIP is associated with distinct spatial covariance patterns on early-phase 18F-FP-CIT PET images, supporting network-level perfusion alterations in DIP.