Synthesis and evaluation of F-18 labeled crizotinib derivative [F-18]FPC as a novel PET probe for imaging c-MET-positive NSCLC tumor
BIOORGANIC & MEDICINAL CHEMISTRY
Authors: Lin, Qingyu; Zhang, Yingying; Fu, Zhequan; Hu, Bingxin; Si, Zhan; Zhao, Yanzhao; Shi, Hongcheng; Cheng, Dengfeng
Abstract
c-MET-positive NSCLC is an important subtype accounting for about 5%similar to 22% of lung cancer. NSCLC patients with activating c-MET are intensively sensitive to c-MET selective receptor tyrosine kinase (RTK) inhibitors, so we aimed to develop a specific PET probe targeting to c-MET-positive NSCLC for potential patients screened by PET/CT. Herein, PET tracer F-18-radiolabeled crizotinib derivative ([F-18]FPC) was successfully achieved through a simple one-step F-18-labeling method. [F-18]FPC PET imaging on c-MET-positive (as well as blocking group) and negative NSCLC models were further evaluated, and results showed that [F-18]FPC was effective as a PET imaging probe that targeted c-MET-positive tumor. Therefore, [F-18]FPC could be a potential PET imaging probe for NSCLC tumor which was sensitive to c-MET-TKIs. By virtue of this property, it will benefit NSCLC patients for c-MET-TKI treatment.
Effect of Resveratrol on Thioacetamide-induced Liver Damage in Rat Models
HEPATITIS MONTHLY
Authors: Hosseini, Sahar; Ebrahimi, Alireza; Bagheri, Fereshteh; Emami, Yasaman; Esmaeilzadeh, Elmira; Azarpira, Negar; Ebrahimi, Sedigheh; Ashkani-Esfahani, Soheil
Abstract
Background: The current treatments of liver diseases are not sufficiently effective, and there has been no therapy that can successfully prevent liver failure and its complications. Previous studies have suggested that resveratrol could inhibit the progression of hepatic diseases based on its antioxidative and anti-inflammatory potentials. Objectives: The present study evaluated the hepato-protective effects of resveratrol in thioacetamide (TAA)-induced acute liverdamage in rats using neurobehavioral and biochemical parameters. Methods: Forty-eight healthy adult Wistar rats were divided into four groups: C1: healthy control group, C2: non-treated liver failure, E1: liver failure treated with resveratrol 5 mg/kg/day, and E2: liver failure treated with resveratrol 10 mg/kg/day. Aspartate aminotransferase/alanine aminotransferase (AST/ALT), alkaline phosphatase (Alk), total bilirubin (TB), and plasma-ammonia (NH4) were analyzed, and histopathological evaluations of the specimens were carried out after sacrificing the models. Hepatic encephalopathy (HE) grading, open-field, elevated plus arms, and forced-swimming tests were performed in the study. Results: The resveratrol-treated groups had lower serum concentrations of NH4, ALT, and AST than the C2 group (P < 0.05). The pathological evaluations demonstrated that resveratrol-treated groups had better outcomes in inflammatory cell infiltration, apoptosis, vacuolization, liver tissue necrosis, and liver damage stage than the C2 group (P < 0.05). They also showed lower grades of HE, higher locomotor activity (open-field test), and diminished levels of depression (forced-swimming) when compared to the C2 group (P < 0.05). Conclusions: Resveratrol supplementation can improve liver damage as AST, ALT, NH4, and tissue damages were decreased after administering the agent in TAA-induced liver damage. Resveratrol can also improve the neurobehavioral manifestations in animal models of liver failure.