Purpose: Parkinson’s disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons in the brain. To achieve better explorations of dopamine changes both centrally and peripherally, we employed uEXPLORER dynamic [11C]CFT PET/CT imaging combined with voxel-wise kinetic modeling. Methods: Eleven participants (five patients, PD and six healthy volunteers, HC) underwent 75-min dynamic scans were enrolled. Volumes of interest for four nigrostriatal nuclei (caudate, putamen, pallidum and substantial nigra) and three digestive organs (pancreas, stomach and duodenum) were delineated. Total-body parametric images of relative transporter rate constant (R1) and distribution volume ratio (DVR) using the simplified reference tissue model (SRTM2) were quantitatively generated by a linear regression with spatial-constraint algorithm. Standardized uptake value ratio (SUVR) at early and late phase were calculated as the semi-quantitative substitutes. Results: Significant differences between the two groups were identified in DVR and SUVRLP of putamen (P < 0.05) and SUVREP of stomach (P < 0.01). For HC group, negative correlations of R1 were achieved between stomach and both putamen and substantial nigra (all P < 0.05); positive correlations of DVR were identified between pancreas and all four brain nuclei (all P < 0.05). Yet in PD group, correlations of R1 or DVR between the targeted digestive and brain areas were considerably diminished. Similar trends in correlations were also found in SUVR analysis. Conclusions: We introduced a pioneering approach using dynamic total-body [11C]CFT PET/CT imaging to investigate distinctive patterns of potential “brain-GI” interplays, which may provide new insights towards the understanding of PD.

Background and purpose: The Chinese medicine monomer solasonine has been shown to be an effective inhibitor of Lung adenocarcinoma in vitro and in vivo. The research on the application of solasonine in lung cancer mostly involves the cell level, the lack of information on the spatial distribution of drugs and related metabolic pathways are common problems faced by many Chinese medicine monomers. Experimental Approach: LC-MS/MS metabolomics analysis was performed to reveal the underlying regulatory mechanism, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and 3D computational reconstruction were applied to illustrated the spatial-temporal distribution of solasonine. Solamargine was chosen as the internal standard to correct the calibration curve due to the similarity in structure. Key Results: Metabolomics analysis illustrated that solasonine promotes A549 cells ferroptosis via GPX4-induced destruction of the glutathione redox system. Detailed distribution features of solasonine in different organs were revealed by MALDI-MSI after intravenous administration in the mice. The heterogeneity of solasonine distribution and penetration in tumor demonstrated that significant drug deposits around the necrotic area. Conclusion and Implication: The anti-tumor mechanism of solasonine associated with ferroptosis is identified for the first time. It provides an additional basis for the previous conclusion that solasonine promotes tumor necrosis. Quantitative spatial-temporal information obtained here can improve our understanding of pharmacokinetics (PK), pharmacodynamics (PD), potential transient toxicities of solasonine in organs, and possibly direct further optimization of drug properties to reduce drug-induced organ toxicity and broaden the scope of application.