Intratumoral metabolic heterogeneity of primary lung tumor in (18)F-FDG PET/CT can predict disease progression after CCRT in inoperable stage III NSCLC.
Radiolabeled lipophilic cationic compounds, such as 18 F-labeled phosphonium salt, accumulate in the mitochondria through a negative inner transmembrane potential. The purpose of this study was to develop and evaluate ( 18 F-fluoropentyl)triphenylphosphonium salt ( 18 F-FPTP) as a myocardial PET agent. Methods: A reference compound of 18 F-FPTP was synthesized via 3-step nucleophilic substitution reactions and was radiolabeled via 2-step nucleophilic substitution reactions of no-carrier-added 18 F-fluoride. Accumulations of 18 F-FPTP, 3 H-tetraphenylphosphonium, and 99m Tc-sestamibi were compared in a cultured embryonic cardiomyoblast cell line (H9c2). The biodistribution of 18 F-FPTP was assessed using BALB/c mice. The 18 F-FPTP small-animal PET study was performed in Sprague-Dawley rats with or without left coronary artery (LCA) ligation. Results: 18 F-FPTP was synthesized with a radiochemical yield of 15%-20% and radiochemical purity of greater than 98%. Specific activity was greater than 6.3 TBq/mmol. Cell uptake of 18 F-FPTP was more than 15-fold higher in H9c2 than in normal fibroblasts (human normal foreskin fibroblasts). Selective collapse of mitochondrial membrane potential substantially decreased cellular uptake for 18 F-FPTP and 3 H-tetraphenylphosphonium, compared with that for 99m Tc-sestamibi. The biodistribution data in mice (n 5 24) showed rapid blood clearance and high accumulation in the heart. Heart-to-blood ratios at 10 and 30 min were 54 and 133, respectively. Heart-to-lung and heart-to-liver ratios at 10, 30, and 60 min were 4, 4, and 7 and 4, 5, and 7, respectively. Dynamic small-animal PET for 60 min after injection of 18 F-FPTP showed an initial spike of radioactivity, followed by retention in the myocardium and rapid clearance from the background. 18 F-FPTP small-animal PET images in LCA-occluded rats demonstrated sharply defined myocardial defects in the corresponding area of the myocardium. The myocardial defect size measured by 18 F-FPTP small-animal PET correlated closely with the hypoperfused area measured by quantitative 2,3,5-triphenyltetrazolium chloride staining (r 2 5 0.92, P , 0.001). Conclusion: The excellent pharmacokinetics of 18 F-FPTP and its correlation with 2,3,5-triphenyltetrazolium chloride staining in normal and LCAoccluded rats suggest that this molecular probe may have a high potential as a mitochondrial voltage sensor for PET. This probe may also allow high throughput, with multiple daily studies and a wide distribution of PET myocardial imaging in the clinic.
2D multiferroics with combined ferroic orders have gained attention owing to their novel functionality and underlying science. Intrinsic ferroelastic–ferroelectric multiferroicity in single‐crystalline van der Waals rhenium dichalcogenides, whose symmetries are broken by the Peierls distortion and layer‐stacking order, is demonstrated. Ferroelastic switching of the domain orientation and accompanying anisotropic properties is achieved with 1% uniaxial strain using the polymer encapsulation method. Based on the electron localization function and bond dissociation energy of the Re–Re bonds, the change in bond configuration during the evolution of the domain wall and the preferred switching between the two specific orientation states are explained. Furthermore, the ferroelastic switching of ferroelectric polarization is confirmed using the photovoltaic effect. The study provides insights into the reversible bond‐switching process and potential applications based on 2D multiferroicity.
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