The overall aim of this study was to evaluate whether iodine-131 radiolabeled monoclonal antibody (mAb) targeting programmed death-ligand 1 (PD-L1) can be used for imaging of PD-L1 expression noninvasively in vivo and playing synergistic effect combined with immunotherapy. Anti-PD-L1 mAb was radiolabeled with iodine-131 ( I-PD-L1 mAb) and was characterized in vitro. Biodistribution and imaging in vivo were performed periodically. Therapy study was conducted in triple-negative breast cancer-bearing BALB/c mice. As results, the labeling efficiencies of I-PD-L1 mAb reached 80% ± 3%, with radiochemical purity of 97% ± 1%. I-PD-L1 mAb preserved the capacity to bind living PD-L1-expressing cells specifically in vitro. Tumor radioactivity uptake of I-PD-L1 mAb was significantly higher than that of control groups. The xenografts were clearly imaged from 48 to 72 hours noninvasively after injection of I-PD-L1 mAb, while the xenografts were not imaged in control groups. Tumor growth was significantly inhibited, and median survival time was remarkably prolonged in combination therapy group compared with control groups. It was concluded that I-PD-L1 mAb can be a potential theranostic candidate for visualizing of PD-L1 expression noninvasively and performing synergistic therapy in carcinomas.
ObjectiveThis study was performed to investigate the efficacy of proximal splenic
artery embolization using detachable balloons for patients with
hypersplenism and portal hypertension.MethodsTwelve patients diagnosed with hypersplenism with thrombocytopenia or
leukocytopenia caused by portal hypertension were treated by proximal
splenic artery embolization with detachable balloons and metallic fibered
coils. All patients were followed for up to 6 months. Blood parameters,
coagulation factors, and liver function indicators were measured. Enhanced
computed tomography and abdominal ultrasonography examinations were also
performed in advance to confirm the infarction area and evaluate the changes
in spleen size.ResultsPostoperative angiography demonstrated complete embolization of the proximal
splenic artery in all 12 patients. Thrombocyte and leukocyte counts rose
significantly in all patients in 2 weeks and stayed significantly higher
than those before embolization throughout the 6-month follow-up. The total
bilirubin concentration and prothrombin activity recovered significantly and
returned to normal levels 6 months later. Computed tomography revealed
partial infarction and liquefaction of the splenic parenchyma in nine
patients.ConclusionsProximal splenic artery embolization using detachable balloons could be
considered a safe and effective therapeutic modality in alleviating
hypersplenism secondary to portal hypertension.
Recently, immune response modulation at the epigenetic level is illustrated in studies, but the possible function of RNA 5-methylcytosine (m5C) modification in cell infiltration within the tumor microenvironment (TME) is still unclear. Three different m5C modification patterns were identified, and high differentiation degree was observed in the cell infiltration features within TME under the above three identified patterns. A low m5C-score, which was reflected in the activated immunity, predicted the relatively favorable prognostic outcome. A small amount of effective immune infiltration was seen in the high m5C-score subtype, indicating the dismal patient survival. Our study constructed a diagnostic model using the 10 signature genes highly related to the m5C-score, discovered that the model exhibited high diagnostic accuracy for PTC, and screened out five potential drugs for PTC based on this m5C-score model. m5C modification exerts an important part in forming the TME complexity and diversity. It is valuable to evaluate the m5C modification patterns in single tumors, so as to enhance our understanding towards the infiltration characterization in TME.
Our study successfully prepared [Ga]DOTA-RRL with a high labeling yield under the optimized reaction conditions and demonstrated its potential role as a PET imaging agent for tumor-targeted diagnosis.
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