Radionuclide-based theranostics - a promising strategy for lung cancer.

PURPOSE: This review aims to provide a comprehensive overview of the latest literature on personalized lung cancer management using different ligands and radionuclide-based tumor-targeting agents. BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide. Due to the heterogeneity of lung cancer, advances in precision medicine may enhance the disease management landscape. More recently, theranostics using the same molecule labeled with two different radionuclides for imaging and treatment has emerged as a promising strategy for systemic cancer management. In radionuclide-based theranostics, the target, ligand, and radionuclide should all be carefully considered to achieve an accurate diagnosis and optimal therapeutic effects for lung cancer. METHODS: We summarize the latest radiotracers and radioligand therapeutic agents used in diagnosing and treating lung cancer. In addition, we discuss the potential clinical applications and limitations associated with target-dependent radiotracers as well as therapeutic radionuclides. Finally, we provide our views on the perspectives for future development in this field. CONCLUSIONS: Radionuclide-based theranostics show great potential in tailored medical care. We expect that this review can provide an understanding of the latest advances in radionuclide therapy for lung cancer and promote the application of radioligand theranostics in personalized medicine.

Protective Effect of Eckol against Acute Hepatic Injury Induced by Carbon Tetrachloride in Mice.

Several in vitro studies have shown the potential hepatoprotective properties of eckol, a natural phlorotannin derived from the brown alga. However, the in vivo hepatoprotective potential of eckol has not been determined. In this study, we performed an in vivo study to investigate the protective effect of eckol and its possible mechanisms on the carbon tetrachloride (CCl4)-induced acute liver injury model in mice. Results revealed that eckol pre-treatment at the dose of 0.5 and 1.0 mg/kg/day for 7 days significantly suppressed the CCl4-induced increases of alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in serum and meliorated morphological liver injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) analysis showed that the number of positive apoptotic hepatocytes in the eckol-treated group was lower than that in the CCl4 model group. Western blotting analysis also demonstrated the enhanced expression of bcl-2 and suppressed expression of cleaved caspase-3 by eckol. The CCl4-induced oxidative stress in liver was significantly ameliorated by eckol, which was characterized by reduced malondialdehyde (MDA) formations, and enhanced superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and glutathione (GSH) content. Moreover, the CCl4-induced elevations of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 were markedly suppressed in the eckol-treated group. However, eckol enhanced the level of IL-10, a potent anti-inflammatory cytokine, and recruited CD11c⁺ dendritic cells into the liver tissues of CCl4-treated mice. These results indicated that eckol has the protective effect on CCl4-induced acute liver injury via multiple mechanisms including anti-apoptosis, anti-oxidation, anti-inflammation and immune regulation.

Preparation of activated carbon from wet sludge by electrochemical-NaClO activation.

Activated carbon (AC) from sludge is one potential solution for sewage sludge disposal, while the drying sludge is cost and time consuming for preparation. AC preparation from the wet sludge with electrochemical-NaClO activation was studied in this work. Three pretreatment processes, i.e. chemical activation, electrolysis and electrochemical-reagent reaction, were introduced to improve the sludge-derived AC properties, and the optimum dosage of reagent was tested from the 0.1:1 to 1:1 (mass rate, reagent:dried sludge). It was shown that the electrochemical-NaClO preparation is the best method under the test conditions, in which AC has the maximum Brunauer, Emmett and Teller area of 436 m²/g at a mass ratio of 0.7. Extracellular polymeric substances in sludge can be disintegrated by electrochemical-NaClO pretreatment, with a disintegration degree of more than 45%. The percentage of carbon decreased from 34.16 to 8.81 after treated by electrochemical-NaClO activation. Fourier transform infrared spectra showed that a strong C-Cl stretching was formed in electrochemical-NaClO prepared AC. The maximum adsorption capacity of AC reaches 109 mg/g on MB adsorption experiment at pH 10 and can be repeated for three times with high removal efficiency after regeneration.

Novel STING-targeted PET radiotracer for alert and therapeutic evaluation of acute lung injury.

Acute lung injury (ALI), as a common clinical emergency, is pulmonary edema and diffuse lung infiltration caused by inflammation. The lack of non-invasive alert strategy, resulting in failure to carry out preventive treatment, means high mortality and poor prognosis. Stimulator of interferon genes (STING) is a key molecular biomarker of innate immunity in response to inflammation, but there is still a lack of STING-targeted strategy. In this study, a novel STING-targeted PET tracer, [18F]FBTA, was labeled with high radiochemical yield (79.7 ± 4.3%) and molar activity (32.5 ± 2.9 GBq/µmol). We confirmed that [18F]FBTA has a strong STING binding affinity (Kd = 26.86 ± 6.79 nmol/L) and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug therapy. Our STING-targeted strategy also reveals that [18F]FBTA can trace ALI before reaching the computed tomography (CT) diagnostic criteria, and demonstrates its better specificity and distribution than [18F]fluorodeoxyglucose ([18F]FDG).

Early Diagnosis of Murine Sepsis-Associated Encephalopathy Using Dynamic PET/CT Imaging and Multiparametric MRI.

PURPOSE: Early diagnosis of sepsis-associated encephalopathy (SAE) is essential for the treatment and prognosis of septic patients. Static PET and MRI have shown promise for early diagnosis, while pharmacokinetic parameters from dynamic PET may provide better quantification for SAE. This study aims to compare the performance of dynamic 2-deoxy-2-[18F]fluoro-D-glucose ([18F]F-FDG) PET and multiparametric MRI in early imaging SAE with a view to providing guidance for the early diagnosis of SAE. PROCEDURES: Dynamic [18F]F-FDG-PET/CT scans and multiparametric MRI were performed in SAE mice induced by LPS. Standardized uptake value (SUV) was measured in static scan images and [18F]F-FDG pharmacokinetic parameters were analyzed with two-tissue compartment model and Patlak plot. MRI relative signal intensity (rT1) derived from T1-weighted images (pre and post contrast) and 4 parameters originating from diffusion-weighted data were measured. RESULTS: Both SUV and dephosphorylation rate constant (k4) increased in SAE model as early as 6 h post sepsis induction, while k4 increased with the relative value (SAE/normal) significantly stronger than that of SUV. Moreover, the net influx constant (Ki) showed significant decrease in SAE as early as 6 h compared with normal mice. Increased signal intensity was identified in T1-weighted contrast enhanced images and rT1 value increased at 12 h post induction. Diffusion tensor imaging (DTI) revealed fractional anisotropy (FA) decreased at 12 h and 24 h in external capsule (ec) and declined axial diffusivity (AD) was shown in white matter at 24 h. CONCLUSIONS: The dynamic PET (k4) was more sensitive than static PET (SUV) for early diagnosis of SAE and declined Ki was firstly found in murine SAE, which indicated the advantage of dynamic PET/CT in early detection and differential diagnosis of SAE. While MRI has a higher soft tissue resolution than PET/CT and can classify more subtle brain areas, the comprehensive utilization of the two modalities is helpful for managing SAE.