Background <p>Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of nigral dopaminergic neurons, which substantially influences the severity of motor and non-motor symptoms. However, the relationship between the regional patterns of striatal dopaminergic loss and specific clinical manifestations remains unclear, as many prior studies relied on global or coarse regional measures without hemispheric resolution or adjustment for handedness. We comprehensively analyzed clinical features in relation to dopamine transporter single-photon emission computed tomography (DAT-SPECT) uptake across 12 atlas-based subregions in a large cohort.</p> Methods <p>We analyzed baseline DAT-SPECT data using ¹²³I-ioflupane in 591 drug-naïve patients with PD and 120 healthy controls from the Parkinson’s Progression Markers Initiative. DAT-SPECT uptake was quantified in 12 anatomically defined striatal subregions. Associations between regional DAT-SPECT uptake and motor and non-motor symptoms were examined using multivariable linear regression models adjusted for age, sex, handedness, and imaging site, with false discovery rate (FDR) correction. Group × region interaction analyses were performed to assess disease specificity.</p> Results <p>In patients with PD, motor symptoms were associated with reduced DAT-SPECT uptake across widespread striatal regions, with right-predominant involvement. Hyposmia was selectively associated with dopaminergic loss across all putaminal subregions, whereas the caudate regions were unaffected. Cognitive performance was associated with the left pre-ventral putamen. No region demonstrated FDR-significant associations in the healthy controls, and several symptom–DAT-SPECT relationships showed significant PD-specific interaction effects.</p> Conclusions <p>12-region DAT-SPECT mapping revealed symptom-specific topographical patterns of striatal dopaminergic dysfunction in drug-naïve patients with PD.</p>