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Pembrolizumab is a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1) found on T and pro-B cells. Pembrolizumab prevents PD-1 ligation by both PD-L1 and PD-L2, preventing the immune dysregulation that otherwise occurs when T cells encounter cells expressing these ligands. Clinically, PD-1 blockade elicits potent anti-tumor immune responses and antibodies blocking PD-1 ligation, including pembrolizumab, have recently received federal drug administration approval for the treatment of advanced melanoma, renal cell cancer, and non-small cell lung cancer. Methods In this study, we evaluated the pharmacokinetics, biodistribution, and dosimetry of pembrolizumab in vivo, accomplished through radiolabeling with positron emitter zirconium-89 (89Zr). Positron emission tomography (PET) imaging was utilized to evaluate the whole-body distribution of 89Zr-Df-Pembrolizumab in two rodent models (mice and rats). Data obtained from PET scans and biodistribution studies were extrapolated to humans to estimate the dosimetry of the tracer. As a proof-of-concept, the biodistribution of 89Zr-Df-Pembrolizumab is further investigated in a humanized murine model. Results The tracer remained stable in blood circulation throughout the study and accumulated the greatest in liver and spleen tissues. Both mice and rats showed similar biodistribution and pharmacokinetics of 89Zr-Df-Pembrolizumab. In the humanized mouse model, T-cell infiltration into the salivary and lacrimal glands could be successfully visualized. Conclusion These data will augment our understanding of the pharmacokinetics and biodistribution of radiolabeled pembrolizumab in vivo, while providing detailed dosimetry data that may lead to better dosing strategies in the future. These findings further demonstrate the utility of noninvasive in vivo PET imaging to dynamically track T-cell checkpoint receptor expression and localization in a humanized mouse model.

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Alcoholic liver disease (ALD) refers to the damages to the liver and its functions due to alcohol overconsumption. It consists of fatty liver/steatosis, alcoholic hepatitis, steatohepatitis, chronic hepatitis with liver fibrosis or cirrhosis, and hepatocellular carcinoma. However, the mechanisms behind the pathogenesis of alcoholic liver disease are extremely complicated due to the involvement of immune cells, adipose tissues, and genetic diversity. Clinically, the diagnosis of ALD is not yet well developed. Therefore, the number of patients in advanced stages has increased due to the failure of proper early detection and treatment. At present, abstinence and nutritional therapy remain the conventional therapeutic interventions for ALD. Moreover, the therapies which target the TNF receptor superfamily, hormones, antioxidant signals, and MicroRNAs are used as treatments for ALD. In particular, mesenchymal stem cells (MSCs) are gaining attention as a potential therapeutic target of ALD. Therefore, in this review, we have summarized the current understandings of the pathogenesis and diagnosis of ALD. Moreover, we also discuss the various existing treatment strategies while focusing on promising therapeutic approaches for ALD.

The rapid developments of implantable biomedical electronics give rise to the motivation of exploring efficient and durable self-powered charging system. In this paper, we report a mesoporous polyvinylidene fluoride (PVDF)-based implantable piezoelectric nanogenerator (NG) for in vivo biomechanical energy harvesting. The NG was built with a sponge-like mesoporous PVDF film and encapsulated by polydimethylsiloxane (PDMS). After embedding this NG into rodents, a Voc of ~200 mV was produced from the gentle movement of rodent muscle. Meanwhile, no toxicity or incompatibility sign was found in the host after carrying the packaged NG for 6 weeks. Moreover, the electric output of this NG was extremely stable and exhibited no deterioration after 5 days of in vivo operation or 1.512 × 108 times mechanical deformation. This NG device could practically output a constant voltage of 52 mV via a 1 µF capacitor under living circumstance. The outstanding efficiency, magnificent durability and exceptional biocompatibility promise this mesoporous PVDF-based NG in accomplishing self-powered bioelectronics with potentially lifespan operation period.