Cellular senescence imaging and senolysis monitoring in cancer therapy based on a ß-galactosidase-activated aggregation-induced emission luminogen.

Cellular senescence is a permanent state of cell cycle arrest characterized by increased activity of senescence associated ß-galactosidase (SA-ß-gal). Notably, cancer cells have been also observed to exhibit the senescence response and are being considered for sequential treatment with pro-senescence therapy followed by senolytic therapy. However, there is currently no effective agent targeting ß-galactosidase (ß-Gal) for imaging cellular senescence and monitoring senolysis in cancer therapy. Aggregation-induced emission luminogen (AIEgen) demonstrates strong fluorescence, good photostability, and biocompatibility, making it a potential candidate for imaging cellular senescence and monitoring senolysis in cancer therapy when endowed with ß-Gal-responsive capabilities. In this study, we introduced a ß-Gal-activated AIEgen named QM-ß-gal for cellular senescence imaging and senolysis monitoring in cancer therapy. QM-ß-gal exhibited good amphiphilic properties and formed aggregates that emitted a fluorescence signal upon ß-Gal activation. It showed high specificity towards the activity of ß-Gal in lysosomes and successfully visualized DOX-induced senescent cancer cells with intense fluorescence both in vitro and in vivo. Encouragingly, QM-ß-gal could image senescent cancer cells in vivo for over 14 days with excellent biocompatibility. Moreover, it allowed for the monitoring of senescent cancer cell clearance during senolytic therapy with ABT263. This investigation indicated the potential of the ß-Gal-activated AIEgen, QM-ß-gal, as an in vivo approach for imaging cellular senescence and monitoring senolysis in cancer therapy via highly specific and long-term fluorescence imaging. STATEMENT OF SIGNIFICANCE: This work reported a ß-galactosidase-activated AIEgen called QM-ß-gal, which effectively imaged DOX-induced senescent cancer cells both in vitro and in vivo. QM-ß-gal specifically targeted the increased expression and activity of ß-galactosidase in senescent cancer cells, localized within lysosomes. It was cleared rapidly before activation but maintained stability after activation in the DOX-induced senescent tumor. The AIEgen exhibited a remarkable long-term imaging capability for senescent cancer cells, lasting over 14 days and enabled monitoring of senescent cancer cell clearance through ABT263-induced apoptosis. This approach held promise for researchers seeking to achieve prolonged imaging of senescent cells in vivo.

Positron Emission Tomography Imaging of Synaptic Dysfunction in Parkinson's Disease.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases with a complex pathogenesis. Aggregations formed by abnormal deposition of alpha-synuclein (αSyn) lead to synapse dysfunction of the dopamine and non-dopamine systems. The loss of dopaminergic neurons and concomitant alterations in non-dopaminergic function in PD constitute its primary pathological manifestation. Positron emission tomography (PET), as a representative molecular imaging technique, enables the non-invasive visualization, characterization, and quantification of biological processes at cellular and molecular levels. Imaging synaptic function with PET would provide insights into the mechanisms underlying PD and facilitate the optimization of clinical management. In this review, we focus on the synaptic dysfunction associated with the αSyn pathology of PD, summarize various related targets and radiopharmaceuticals, and discuss applications and perspectives of PET imaging of synaptic dysfunction in PD.

Therapeutic potential of tumor treating fields for malignant brain tumors.

BACKGROUND: Malignant brain tumors are among the most threatening diseases of the central nervous system, and despite increasingly updated treatments, the prognosis has not been improved. Tumor treating fields (TTFields) are an emerging approach in cancer treatment using intermediate-frequency and low-intensity electric field and can lead to the development of novel therapeutic options. RECENT FINDINGS: A series of biological processes induced by TTFields to exert anti-cancer effects have been identified. Recent studies have shown that TTFields can alter the bioelectrical state of macromolecules and organelles involved in cancer biology. Massive alterations in cancer cell proteomics and transcriptomics caused by TTFields were related to cell biological processes as well as multiple organelle structures and activities. This review addresses the mechanisms of TTFields and recent advances in the application of TTFields therapy in malignant brain tumors, especially in glioblastoma (GBM). CONCLUSIONS: As a novel therapeutic strategy, TTFields have shown promising results in many clinical trials, especially in GBM, and continue to evolve. A growing number of patients with malignant brain tumors are being enrolled in ongoing clinical studies demonstrating that TTFields-based combination therapies can improve treatment outcomes.

Evaluation of medical services from the perspective of COVID-19 vaccine demand satisfaction in Hangzhou, China.

The outbreak of COVID-19 has had a huge global impact, and it continues to test the resilience of medical services to emergencies worldwide. In the current post-epidemic era, vaccination has become a highly effective strategy to prevent the spread of COVID-19. However, using conventional mathematical models to evaluate the spatial distribution of medical resources, including vaccination, ignore people's behaviors and choices and make simplifications to the real world. In this study, we use an enhanced model based on the Theory of People Behavior (TPB) to perform a macro analysis of the satisfaction ability of medical resources for vaccination in Hangzhou, China, and attribute the city to a three-level structure. According to the allocation, the supply capacity of vaccination sites is calculated and divided into four categories (good, normal, not bad, and bad). Meanwhile, we raise an assumption based on the result and the general development law of the city and analyze the reasons for the impact of personal behavior on the spatial distribution of medical resources, as well as the relationship between the demand distribution and spatial distribution of medical resources and future development strategies. It is considered that the overall medical resources, especially vaccination in Hangzhou, feature the situation of central supply overflow, and are found to hardly meet the needs of population points in surrounding areas, requiring a more flexible strategy to allocate facilities in these areas.

Highly Efficient Radiosynthesis and Biological Evaluation of [18 F]Safinamide, a Radiolabelled Anti-Parkinsonian Drug for Positron Emission Tomography Imaging.

As an add-on drug approved for Parkinson's disease treatment, safinamide has multiple functions, such as selective and reversible monoamine oxidase-B inhibition, voltage-sensitive sodium/potassium channel blockage, and glutamate release inhibition. Meanwhile, safinamide shows tremendous therapeutic potential in the context of other central nervous system diseases (e. g. ischaemic stroke, amyotrophic lateral sclerosis, depression, etc.). In this work, [18 F]safinamide, which is safinamide labelled by the positron-emitting radionuclide [18 F]fluorine, was synthesized automatically based on iodonium ylide precursors with high radiochemical yield and high molar activity. Density functional theory was applied to calculate the Gibbs free energy change during iodonium ylide-mediated fluorination and to interpret the effect of tetraethylammonium (TEA+ ) as the counter cation in these reactions to improve the nucleophilicity of [18 F/19 F]fluoride. In addition, positron emission tomography studies on Sprague Dawley rats were carried out to determine the imaging characteristics, pharmacokinetics, and metabolism of the [18 F]safinamide radiotracer. The results displayed the complete biodistribution of the radiotracer, especially in rat brains, and revealed that [18 F]safinamide has moderate brain uptake, rapid and reversible binding kinetics, and good stability.

Optical molecular imaging and theranostics in neurological diseases based on aggregation-induced emission luminogens.

Optical molecular imaging and image-guided theranostics benefit from special and specific imaging agents, for which aggregation-induced emission luminogens (AIEgens) have been regarded as good candidates in many biomedical applications. They display a large Stokes shift, high quantum yield, good biocompatibility, and resistance to photobleaching. Neurological diseases are becoming a substantial burden on individuals and society that affect over 50 million people worldwide. It is urgently needed to explore in more detail the brain structure and function, learn more about pathological processes of neurological diseases, and develop more efficient approaches for theranostics. Many AIEgens have been successfully designed, synthesized, and further applied for molecular imaging and image-guided theranostics in neurological diseases such as cerebrovascular disease, neurodegenerative disease, and brain tumor, which help us understand more about the pathophysiological state of brain through noninvasive optical imaging approaches. Herein, we focus on representative AIEgens investigated on brain vasculature imaging and theranostics in neurological diseases including cerebrovascular disease, neurodegenerative disease, and brain tumor. Considering different imaging modalities and various therapeutic functions, AIEgens have great potential to broaden neurological research and meet urgent needs in clinical practice. It will be inspiring to develop more practical and versatile AIEgens as molecular imaging agents for preclinical and clinical use on neurological diseases.

Visualization of Mitochondria During Embryogenesis in Zebrafish by Aggregation-Induced Emission Molecules.

PURPOSE: Aggregation-induced emission (AIE) molecules have been widely utilized for fluorescence imaging in many biomedical applications, benefited from large Stokes shift, high quantum yield, good biocompatibility, and resistance to photobleaching. And visualization of mitochondria is almost investigated in vitro and ex vivo, but in vivo study of mitochondria is more essential for systematic biological research, especially during embryogenesis. Therefore, suitable and time-saving alternatives with simple operation based on AIE molecules are urgently needed compared with traditional transgenic approach. PROCEDURES: Five tetraphenylethylene isoquinolinium (TPE-IQ)-based molecules with AIE characteristics and their ability of mitochondrial visualization in vitro and in vivo and mitochondrial tracking during embryogenesis on zebrafish model were investigated. The biosafety of these AIE molecules was also evaluated systematically in vitro and in vivo. RESULTS: All these five AIE molecules could image mitochondria in vitro with good biocompatibility. In them, TPE-IQ1 exhibited excellent imaging quality for in vivo visualization and tracking of mitochondria during the 4-day embryogenesis in zebrafish, in comparison with the conventional transgenic fluorescent protein. Furthermore, TPE-IQ1 could visualize mitochondrial damage induced by chemicals in real time on 24-h post fertilization (hpf) embryos. CONCLUSIONS: This study indicated TPE-IQ-based AIE molecules had the potential for mitochondrial imaging and tracking during embryogenesis and mitochondrial damage visualization in vivo.

Positron emission tomography in the COVID-19 pandemic era.

Coronavirus disease 2019 (COVID-19) has become a major public health problem worldwide since its outbreak in 2019. Currently, the spread of COVID-19 is far from over, and various complications have roused increasing awareness of the public, calling for novel techniques to aid at diagnosis and treatment. Based on the principle of molecular imaging, positron emission tomography (PET) is expected to offer pathophysiological alternations of COVID-19 in the molecular/cellular perspectives and facilitate the clinical management of patients. A number of PET-related cases and research have been reported on COVID-19 over the past one year. This article reviews the current studies of PET in the diagnosis and treatment of COVID-19, and discusses potential applications of PET in the development of management strategy for COVID-19 patients in the pandemic era.