Feasibility of a single-day protocol for SPECT and PET assessment of dopamine transporter availability, cardiac innervation and metabolic patterns in patients with movement disorders

Abstract Purpose Due to new advances in molecular and imaging biomarkers, a biological classification of Parkinson’s disease (PD) called SyNeurGe (Hoglinger et al. Lancet Neurol 2024;23:191-204) has been proposed for research use recently. [123I]ioflupane dopamine transporter single-photon-emission-computed tomography (DaT-SPECT) and cardiac [123I]meta-iodobenzylguanidine (MIBG) scintigraphy are included in this biological classification scheme together with 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) as central imaging biomarkers for the assessment of dopaminergic function, cardiac sympathetic denervation, and metabolic patterns in brain. In order to facilitate this prospectively high imaging demand and optimize diagnostic workup in PD we propose a single-day protocol. Methods First, we excluded relevant binding of MIBG in the brain as well as DaT in the heart by acquisition of brain scans in patients that received MIBG as well as by acquisition of chest scans in patients that received DaT. Then, we performed a single-day protocol including DaT-SPECT and cardiac MIBG scintigraphy in ten patients with clinically suspected α-synucleinopathies (9 male, 1 female; 68.2 ± 7.3 years). Both radiotracers were injected simultaneously and cardiac imaging was performed at 3.5 h after injection followed by brain imaging at 4 h after injection using standard protocols for MIBG-scintigraphy and DaT-SPECT. Additionally, five patients of the dual tracer protocol group received brain FDG-PET after DaT and MIBG imaging. Results Single tracer imaging confirmed no relevant uptake of [123I]ioflupane in the heart or [123I]MIBG in the brain. Six out of the ten dual tracer protocol patients (PD or multiple system atrophy with Parkinsonian phenotype (MSA-P)) showed a significantly reduced DaT-SPECT binding (z-score < -2) in at least one hemisphere (mean putaminal z-score -4.01 ± 1.39) while seven patients had a pathological heart-to-mediastinum ratio in the MIBG scan (mean H/M-ratio: 1.12 ± 0.08). Both DaT and MIBG scans could visually be interpreted without any signs of image artifacts or decrease in imaging quality and also quantitatively did not reveal significant differences to the single tracer scans. FDG-PET brain scans of the triple tracer protocol patients also showed no relevant interference in regard to image quality as well was generation of surface projections and z-scores. Conclusion A single day protocol for DaT-SPECT, MIBG, and FDG-PET facilitates biomarker assessments needed for efficient biological characterization of Parkinsonian syndromes according to the SyNeurGe criteria.