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PURPOSE: NB12 is a bispecific antibody that consists of two anti-programmed cell death-ligand 1 (PD-L1) nanobodies and two anti-programmed cell death-ligand 2 (PD-L2) nanobodies. The aim of this study was to design a novel tracer, [124I]I-NB12, targeting PD-L1/2 and perform preclinical evaluations to dynamically monitor PD-L1/2 expression for determining cancer patient responsiveness to ICI therapy. METHODS: NB12 was labelled with the radionuclide 124I at room temperature (RT). An in vitro binding assay was performed to assess the affinity of [124I]I-NB12 for PD-L1 and PD-L2. Cellular uptake, pharmacokinetic, and biodistribution experiments were performed to evaluate the biological properties. Micro-PET/CT imaging with [124I]I-NB12 was conducted at different time points. Immunohistochemical and haematoxylin and eosin (HE) staining experiments were carried out using tumour tissues. Routine blood, biochemical indices and major organ pathology were used to evaluate the biosafety of the tracers. RESULTS: The radiochemical yield of [124I]I-NB12 was 84.62 ± 3.90%, and the radiochemical purity (RCP) was greater than 99%. [124I]I-NB12 had a high affinity for the PD-L1 (Kd = 19.82 nM) and PD-L2 (Kd = 2.93 nM). Cellular uptake experiments confirmed that the uptake of [124I]I-NB12 by A549-PDL1/2 cells was greater than that by A549 cells. The half-lives of the distribution phase and elimination phase were 0.26 h and 4.08 h, respectively. Micro-PET/CT showed significant [124I]I-NB12 uptake in the tumour region of A549-PDL1/2 tumour-bearing mice compared with A549 tumour-bearing mice 24 h postinjection. Immunohistochemical and HE staining experiments confirmed that tumour-bearing mice was successfully constructed. CONCLUSION: We constructed a bispecific antibody that targets PD-L1 and PD-L2, namely, [124I]I-NB12. Biological evaluation revealed its specificity and affinity for PD-L1/2, and micro-PET/CT confirmed the feasibility of visualizing tumour PD-L1/2 in vivo. Using [124I]I-NB12 may be a promising strategy for identifying cancer patients that can potentially benefit from ICI therapy.
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This study investigated the impact of varying total ammonia nitrogen (TAN) feed levels along with water temperature decreases on the performance of nitrifying moving bed biofilm reactor (MBBR) at 1 °C and its recovery at 3 °C. Five MBBR reactors were operated with different TAN concentrations as water temperature decreased from 20 to 3 °C: reactor R1 at 30 mg N/L, reactor R2 at 20 mg N/L, reactor R3 at 15 mg N/L, reactor R4 at 10 mg N/L and reactor R5 at 0 mg N/L. The corresponding biofilm characteristics were also analyzed to understand further nitrifying MBBR under different TAN feeding scenarios. The findings revealed that the higher TAN levels were before reaching 1 °C, the better nitrification performance and the more biomass grew. However, the highest TAN concentration (30 mg N/L) might negatively affect the nitrification performance, the activity of nitrifiers, and the growth of biofilms at 1 °C because of the toxic effects of un-ionized or free ammonia (FA). It was observed that the activities of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) were affected by FA concentrations ranging from 0.2 to 0.7 mg N/L at 1 °C, but they could gradually be adapted to such inhibitory environment, with NOB recovering more quickly and robustly than AOB. The study identified 20 mg N/L (67 % of maximum influent TAN at 1 °C in R2 as the optimal TAN feeding concentration, achieving over 90 % TAN removal and a surface area removal rate (SARR) of 0.78 ± 0.02 g N/m2·d at 1 °C. Meanwhile, R2 also exhibited the highest biofilm mass, with total solids at 13.3 mg/carrier and volatile solids at 11.3 mg/carrier. As TAN was removed, nitrite accumulation was observed at 1 °C, and higher influent TAN concentrations prior to 1 °C appeared to delay the accumulation. When water temperature increased from 1 °C to 3 °C, nitrification performance improved significantly in all reactors without nitrite accumulation, and the higher TAN feeding in the previous stage led to faster recovery. Compared with 20 °C, biofilm became thinner and denser at 1 °C and 3 °C. Furthermore, this study revealed significant shifts in microbial community composition and nitrifier abundances in response to changes in water temperature and influent TAN levels. The dominant nitrifiers were identified as Nitrosomonadaceae (AOB) and Nitrospiraceae (NOB). At 1 °C, the nitrifier abundances were significantly correlated with SARRs, FA, and biofilm density. R2, which exhibited the best nitrification performance, maintained higher nitrifier abundances at 1 °C.
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Amoníaco , Biopelículas , Reactores Biológicos , Nitrificación , Amoníaco/metabolismo , Temperatura , Eliminación de Residuos Líquidos/métodos , Bacterias/metabolismo , Nitritos/metabolismo , Nitrógeno/metabolismoRESUMEN
The aim of this study is to combine flaxseed oil (FO), rich in α-linolenic acid (ALA), with Sunite sheep tail fat (STF) through a lipase-catalyzed transesterification reaction, in order to produce an edible oil with a fatty acid ratio suitable for human needs. Initially, the optimal conditions for esterification were determined using the Box-Behnken design, with the measurement criterion being the content of ALA at the sn-2 position. The results indicated that the highest content of sn-2 ALA was obtained under the conditions of using 6.8 wt% Lipozyme®RMIM as the catalyst, a reaction temperature of 57°C, a reaction time of 3.3 h, and a substrate mass ratio of 5.6:4.4 for STF and FO. This led to the rapid breaking and recombining of molecular bonds, resulting in the interesterified fat (IF) with the highest content of ALA at the sn-2 position. Comparing STF and FO, IF exhibited excellent fatty acid composition and content. Furthermore, IF had a lower melting point and crystallization temperature compared to STF, and its solid fat content decreased with increasing temperature, completely melting at temperatures above 30°C. Thus, IF is a synthesized fat with excellent properties from both animal and vegetable sources.
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Objective: To investigate the relationship between dietary inflammatory index (DII) scores and infertility in US adults aged 18 to 45. Methods: Data were gathered from the 2013-2018 National Health and Nutrition Examination Survey (NHANES). In total, 3496 women were included in the study. To examine the relationship between DII, EDII and infertility, a weighted multivariable logistic regression analysis using continuous factors or categorical variables grouped by quartiles was conducted. Using subgroup analysis stratified based on DII and infertility features, the association between DII and infertility has been further studied. In order to determine whether there was a nonlinear relationship between DII and infertility, restricted cubic spline (RCS) analysis was carried out. Results: For statistical analysis, a total of 3496 individuals - 367 patients with infertility and 3129 persons without infertility - were included. A multivariable logistic regression study revealed a positive relationship between DII and infertility. A significant difference in subgroup analysis was shown in age group and race, although RCS analysis demonstrated nonlinear relationship between the DII and infertility. Conclusion: For participants aged 18-45 years, higher DII scores were positively correlated with infertility. In addition, anti-inflammatory diets might improve infertility outcomes.
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Dieta , Infertilidad Femenina , Inflamación , Encuestas Nutricionales , Humanos , Femenino , Adulto , Inflamación/epidemiología , Adulto Joven , Adolescente , Infertilidad Femenina/epidemiología , Persona de Mediana Edad , Estados Unidos/epidemiología , Estudios TransversalesRESUMEN
BACKGROUND: The impact of bacterial vaginosis on women's health is an increasing concern; however, the effect of the obesity index on bacterial vaginosis is controversial. We investigated the association between body mass index and bacterial vaginosis in women in the United States. METHODS: This was a cross-sectional study which obtained the data from the National Health and Nutrition Examination Survey from 2001 to 2004, in which weighted multivariate regression and logistic regression analyses were performed to explore the independent relationship between body mass index and bacterial vaginosis. Subgroup analyses and smoothed curve fitting were also performed. RESULTS: A total of 5,428 participants were enrolled, and the findings show that the participants with higher body mass index tended to have a higher incidence of bacterial vaginosis. In the fully adjusted model, a positive association between bacterial vaginosis and body mass index was observed (Odd's ratio = 1.03, 95% Confidence interval, 1.01-1.04). The subgroup analysis showed that this positive association was significant in non-Hispanic White individuals (Odd's ratio = 1.0327, 95% Confidence interval, 1.0163, 1.0493). CONCLUSION: Increased bacterial vaginosis positivity may be associated with an increased body mass index.
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Índice de Masa Corporal , Encuestas Nutricionales , Vaginosis Bacteriana , Humanos , Vaginosis Bacteriana/epidemiología , Vaginosis Bacteriana/microbiología , Femenino , Adulto , Estudios Transversales , Estados Unidos/epidemiología , Prevalencia , Persona de Mediana Edad , Adulto Joven , Obesidad/epidemiología , Obesidad/complicacionesRESUMEN
Pancreatic ductal adenocarcinoma (PDAC), which has a poor prognosis and nonspecific symptoms and progresses rapidly, is the most common pancreatic cancer type. Inhibitors targeting KRAS G12D and G12C mutations have been pivotal in PDAC treatment. Cancer cells with different KRAS mutations exhibit various degrees of glutamine dependency; in particular, cells with KRAS G12D mutations exhibit increased glutamine uptake. (2S,4R)-4-[18F]FGln has recently been developed for clinical cancer diagnosis and tumor cell metabolism analysis. Thus, we verified the heterogeneity of glutamine dependency in PDAC models with different KRAS mutations by a visual and noninvasive method with (2S,4R)-4-[18F]FGln. Two tumor-bearing mouse models (bearing the KRAS G12D or G12C mutation) were injected with (2S,4R)-4-[18F]FGln, and positron emission tomography (PET) imaging features and biodistribution were observed and analyzed. The SUVmax in the regions of interest (ROI) was significantly higher in PANC-1 (G12D) tumors than in MIA PaCa-2 (G12C) tumors. Biodistribution analysis revealed higher tumor accumulation of (2S,4R)-4-[18F]FGln and other metrics, such as T/M and T/B, in the PANC-1 mouse models compared to those in the MIAPaCa-2 mouse models. In conclusion, PDAC cells with the KRAS G12D and G12C mutations exhibit various degrees of (2S,4R)-4-[18F]FGln uptake, indicating that (2S,4R)-4-[18F]FGln might be applied to detect KRAS G12C and G12D mutations and provide treatment guidance.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animales , Ratones , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/genética , Glutamina/metabolismo , Glutamina/farmacología , Mutación , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Distribución Tisular , Radioisótopos de Flúor/química , Radioisótopos de Flúor/farmacologíaRESUMEN
T cell immunoglobulin and mucin domain-3 (TIM3; HAVCR2) is a transmembrane protein that exerts negative regulatory control over T cell responses. Studies have demonstrated an upregulation of TIM3 expression in tumor-infiltrating lymphocytes (TILs) in cancer patients. In this investigation, a series of monoclonal antibodies targeting TIM3 were produced by hybridoma technology. Among them, C23 exhibited favorable biological properties. To enable specific binding, we developed a 124I/125I-C23 radio-tracer via N-bromosuccinimide (NBS)-mediated labeling of the monoclonal antibody C23. Binding affinity and specificity were assessed using the 293T-TIM3 cell line, which overexpresses TIM3, and the parent 293T cells. Furthermore, biodistribution and in vivo imaging of 124I/125I-C23 were examined in HEK293TIM3 xenograft models and allograft models of 4T1 (mouse breast cancer cells) and CT26 (mouse colon cancer cells). Micro-PET/CT imaging was conducted at intervals of 4, 24, 48, 72, and/or 96 h post intravenous administration of 3.7-7.4 MBq 124I-C23 in the respective model mice. Additionally, immunohistochemistry (IHC) staining of TIM3 expression in dissected tumor organs was performed, along with an assessment of the corresponding expression of Programmed Death 1 (PD1), CD3, and CD8 in the tumors. The C23 monoclonal antibody (mAb) specifically binds to TIM3 protein with a dissociation constant of 23.28 nM. The 124I-C23 and 125I-C23 radio-tracer were successfully prepared with a labeling yield of 83.59 ± 0.35% and 92.35 ± 0.20%, respectively, and over 95.00% radiochemical purity. Stability results indicated that the radiochemical purity of 124I/125I-C23 in phosphate-buffered saline (PBS) and 5% human serum albumin (HSA) was still >80% after 96 h. 125I-C23 uptake in 293T-TIM3 cells was 2.80 ± 0.12%, which was significantly higher than that in 293T cells (1.08 ± 0.08%), and 125I-C23 uptake by 293T-TIM3 cells was significantly blocked at 60 and 120 min in the blocking groups. Pharmacokinetics analysis in vivo revealed an elimination time of 14.62 h and a distribution time of 0.4672 h for 125I-C23. Micro-PET/CT imaging showed that the 124I-C23 probe uptake in the 293T-TIM3 model significantly differed from that of the negative control group and blocking group. In the humanized mouse model, the 124I-C23 probe had obvious specific uptake in the 4T1 and CT26 models and maximum uptake at 24 h in tumor tissues (SUVmax (the maximum standardized uptake value) in 4T1 and CT26 humanized TIM3 murine tumor models: 0.59 ± 0.01 and 0.76 ± 0.02, respectively). Immunohistochemistry of tumor tissues from these mouse models showed comparable TIM3 expression. CD3 and CD8 cells and PD-1 expression were also observed in TIM3-expressing tumor tissues. The TIM3-targeting antibody C23 showed good affinity and specificity. The 124I/125I-C23 probe has obvious targeting specificity for TIM3 in vitro and in vivo. Our results suggest that 124I/125I-C23 is a promising tracer for TIM3 imaging and may have great potential in monitoring immune checkpoint drug efficacy.
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Anticuerpos Monoclonales , Neoplasias , Animales , Humanos , Ratones , Anticuerpos Monoclonales/química , Línea Celular Tumoral , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Radioisótopos de Yodo , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos/farmacocinética , Distribución TisularRESUMEN
Extracellular matrix metalloproteinase inducer CD147 is a glycoprotein on the cell surface. There is minimal expression of CD147 in normal epithelial and fetal tissues, but it is highly expressed in a number of aggressive tumors. CD147 has been implicated in pan-cancer immunity and progression. With the development of CD147-targeting therapeutic strategy, accurate detection of CD147 expression in tumors and its changes during the therapy is necessary. In this study we constructed a novel radiotracer by labeling the anti-CD147 mAb with radionuclide 124/125I (124/125I-anti-CD147) for noninvasive detection of CD147 expression in pan-cancers, and characterized its physicochemical properties, affinity, metabolic characteristics, biodistribution and immunoPET imaging with 124I-IgG and 18F-FDG as controls. By examining the expression of CD147 in cancer cell lines, we found high CD147 expression in colon cancer cells LS174T, FADU human pharyngeal squamous cancer cells and 22RV1 human prostate cancer cells, and low expression of CD147 in human pancreatic cancer cells ASPC1 and human gastric cancer cells BGC823. 124/125I-anti-CD147 was prepared using N-bromine succinimide (NBS) as oxidant and purified by PD-10 column. Its radiochemical purity (RCP) was over 99% and maintained over 85% in saline or 5% human serum albumin (HSA) for more than 7 d; the RCP of 125I-anti-CD147 in blood was over 90% at 3 h post injection (p.i.) in healthy mice. The Kd value of 125I-anti-CD147 to CD147 protein was 6.344 nM, while that of 125I-IgG was over 100 nM. 125I-anti-CD147 showed much greater uptake in CD147 high-expression cancer cells compared to CD147 low-expression cancer cells. After intravenous injection in healthy mice, 125I-anti-CD147 showed high initial uptake in blood pool and liver, the uptake was decreased with time. The biological half-life of distribution and clearance phases in healthy mice were 0.63 h and 19.60 h, respectively. The effective dose of 124I-anti-CD147 was estimated as 0.104 mSv/MBq. We conducted immunoPET imaging in tumor-bearing mice, and demonstrated a significantly higher tumor-to-muscle ratio of 124I-anti-CD147 compared to that of 124I-IgG and 18F-FDG in CD147 (+) tumors. The expression levels of CD147 in cells and tumors were positively correlated with the maximum standardized uptake value (SUVmax) (P < 0.01). In conclusion, 124/125I-anti-CD147 displays high affinity to CD147, and represents potential for the imaging of CD147-positive tumors. The development of 124I-anti-CD147 may provide new insights into the regulation of tumor microenvironment and formulation of precision diagnosis and treatment programs for tumors.
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Fluorodesoxiglucosa F18 , Neoplasias de la Próstata , Masculino , Humanos , Ratones , Animales , Distribución Tisular , Radiofármacos , Radioisótopos de Yodo , Inmunoglobulina G , Línea Celular Tumoral , Microambiente TumoralRESUMEN
OBJECTIVE: This study aimed to compare the efficacy of enhanced 3D T1-weighted black-blood fast-spin-echo vessel wall magnetic resonance imaging (eVW-MRI) and time-of-flight magnetic resonance angiography (TOF MRA) for follow-up evaluation of aneurysms treated with flow diversion (FD). METHODS: Our study enrolled 77 patients harboring 84 aneurysms treated with FD. Follow-up was by MRI (eVW-MRI and TOF MRA) and digital subtraction angiography (DSA). Two radiologists, blinded to DSA examination results, independently evaluated the images of aneurysm occlusion and parent artery patency using the Kamran-Byrne Scale. Interobserver diagnostic agreement and intermodality diagnostic agreement were acquired. Pretreatment and follow-up aneurysm wall enhancement (AWE) patterns were collected. RESULTS: Based on the Kamran-Byrne Scale, the intermodality agreement between eVW-MRI and DSA was better than TOF MRA versus DSA for aneurysm remnant detection (weighted ĸ = 0.891 v. 0.553) and parent artery patency (ĸ = 0.950 v. 0.221). Even with the coil artifact, the consistency of eVW-MRI with DSA for aneurysm remnant detection was better than that of TOF MRA (weighted ĸ = 0.891 v. 0.511). The artifact of adjunctive coils might be more likely to affect the accuracy in evaluating parent artery patency with TOF MRA than with eVW-MRI (ĸ = 0.077 v. 0.788). The follow-up AWE patterns were not significantly associated with pretreatment AWE patterns and aneurysm occlusion. CONCLUSIONS: The eVW-MRI outperforms TOF MRA as a reliable noninvasive and nonionizing radioactive imaging method for evaluating aneurysm remnants and parent artery patency after FD. The significance of enhancement patterns on eVW-MRI sequences needs more exploration. CLINICAL RELEVANCE STATEMENT: The application of enhanced vessel wall magnetic resonance imaging has proven to be a promising tool to depict aneurysm remnant and parent artery stenosis in order to tailor the antiplatelet therapy strategy in patients after flow diversion. KEY POINTS: ⢠Enhanced vessel wall magnetic resonance imaging has an emerging role in depicting aneurysm remnant and parent artery patency after flow diversion. ⢠With or without the artifact from adjunctive coils, enhanced vessel wall magnetic resonance imaging was better than TOF MRA in detecting aneurysm residual and parent artery stenosis by using DSA imaging as the standard. ⢠Enhanced vessel wall magnetic resonance imaging holds potential to be used as an alternative to DSA for routine aneurysm follow-up after flow diversion.
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Embolización Terapéutica , Aneurisma Intracraneal , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Estudios de Seguimiento , Resultado del Tratamiento , Constricción Patológica/terapia , Embolización Terapéutica/métodos , Imagen por Resonancia Magnética , Angiografía por Resonancia Magnética/métodos , Angiografía de Substracción Digital/métodosRESUMEN
RATIONALE AND OBJECTIVES: This project aims to investigate the diagnostic performance of multiple overlapping-echo detachment imaging (MOLED) technique-derived transverse relaxation time (T2) maps in predicting progesterone receptor (PR) and S100 expression in meningiomas. MATERIALS AND METHODS: 63 meningioma patients were enrolled from October 2021 to August 2022, who underwent a complete routine magnetic resonance imaging and T2 MOLED, which can characterize the whole brain transverse relaxation time within 32 seconds in a single scan. After the surgical resection of meningiomas, the expression levels of PR and S100 were determined by an experienced pathologist using immunohistochemistry techniques. Histogram analysis was performed in tumor parenchyma based on the parametric maps. Independent t test and Mann-Whitney U test were applied for the comparison of histogram parameters between different groups, with a significance level of P < .05. Logistic regression and receiver operating characteristic (ROC) analysis with 95% confidence interval were conducted for the diagnostic efficiency evaluation. RESULTS: PR-positive group had significantly elevated T2 histogram parameters (P = .001-.049) compared to the PR-negative group. The multivariate logistic regression model with T2 showed the highest area under the ROC curve (AUC) for predicting PR expression (AUC=0.818). Additionally, the multivariate model also had the best diagnostic performance for predicting meningioma S100 expression (AUC=0.768). CONCLUSION: The MOLED technique-derived T2 maps can distinguish PR and S100 status in meningiomas preoperatively.
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Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/diagnóstico por imagen , Meningioma/cirugía , Meningioma/patología , Imagen de Difusión por Resonancia Magnética/métodos , Estudios Prospectivos , Receptores de Progesterona , Imagen por Resonancia Magnética/métodos , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: The tolerance of cervical cancer to radiotherapy is a major factor affecting treatment outcomes. The miR-214-5p is involved in the regulation of biological processes such as tumor proliferation and metastasis. OBJECTIVES: The aim of the study was to explore the role of miR-214-5p and Rho-associated coiled-coil containing protein kinase 1 (ROCK1) in cervical cancer and their response to radiotherapy in cervical cancer patients. MATERIAL AND METHODS: Fifty-three cervical cancer tissue samples were collected to analyze the level of miR-214-5p in patients with different responses to radiotherapy. Cervical cancer cell lines with radiation resistance were selected to explore the role of miR-214-5p in radiosensitivity. The wound healing, transwell migration, clone formation assay, and in vivo analysis were utilized to evaluate the effect of miR-214-5p on the radiation sensitivity of cervical cancer cells. RESULTS: Patients with poor radiotherapy responses demonstrated low levels of miR-214-5p. The upregulation of miR-214-5p decreased migration and invasion ability of radiotherapy-resistant cells. The bioinformatic analysis showed that ROCK1 is a candidate target gene of miR-214-5p, and this was confirmed with dual luciferase reporter assay showing that miR-214-5p directly interacts with the 3'untranslated region (3'UTR) of ROCK1. Decreased ROCK1 improved the radiosensitivity of cervical cancer in vitro and in vivo, and the overexpression of ROCK1 decreased the radiosensitivity effect of miR-214-5p in cervical cancer cells. CONCLUSIONS: The miR-214-5p can regulate the radiation sensitivity of cervical cancer cells by targeting the mRNA of ROCK1 and regulating its expression.
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MicroARNs , Neoplasias del Cuello Uterino , Femenino , Humanos , MicroARNs/genética , Neoplasias del Cuello Uterino/patología , Quinasas Asociadas a rho/genética , Quinasas Asociadas a rho/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Tolerancia a Radiación , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genéticaRESUMEN
BACKGROUND AND PURPOSE: Some kinds of antibody-drug conjugate (ADC) with high affinity to Nectin-4 have demonstrated breakthrough progress in the third-line setting for bladder cancer. However, many patients are still difficult to benefit from treatment based on the heterogeneity of tumour. As the most advanced auxiliary treatment technology, treatment visualization can most intuitively predict the effectiveness of drug treatment, and timely detect the occurrence of drug resistance. Among them, nuclear medicine molecular probes play an important role in this field. METHODS: 124/125I-EV was prepared by labelling Enfortumad Vedetin (EV), an ADC drugs widely used in clinic targeted Nectin-4, with Na124/125I using N-bromine succinimide as oxidant. The radiochemical purity was analyzed via radio-TLC and bioactivity was measured by enzyme-linked immunosorbent assay. Cell uptake assay and small-animal PET imaging were performed to verified the specificity and targeting. KEY RESULTS: 124/125I-EV was prepared with high labeling yield and radiochemical purity. ELISA assays demonstrated that 124I-EV maintained the same high bioactivity as EV with significantly higher uptake in SW780 cells (Nectin-4 positive, 4.05 ± 0.32 %IA/5 × 105 cells at 8 h) than that in T24 cells (Nectin-4 negative, 1.34 ± 0.18 %IA/5 × 105 cells, p < 0.001). In PET imaging, 124I-EV had a significantly higher accumulation in SW780 tumour than that in T24 tumour and the uptake in SW780 tumour could be specifically blocked when co-injected with cold EV. The signal-to-noise ratio at the tumour site gradually increased with time, and peaked at 72 h. CONCLUSION AND IMPLICATIONS: 124I-EV was successfully prepared with high specificity and binding affinity of Nectin-4. This radioactive probe completely simulates the internal circulation of ADC drugs and tumour uptake and retention, which will greatly improve the clinical application of ADC therapy.
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Carcinoma de Células Transicionales , Inmunoconjugados , Radioisótopos de Yodo , Yodo , Neoplasias de la Vejiga Urinaria , Animales , Humanos , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , NectinasRESUMEN
RATIONALE AND OBJECTIVES: Stroke patients commonly face challenges during magnetic resonance imaging (MRI) examinations due to involuntary movements. This study aims to overcome these challenges by utilizing multiple overlapping-echo detachment (MOLED) quantitative technology. Through this technology, we also seek to detect microstructural changes of the normal-appearing corticospinal tract (NA-CST) in subacute-chronic stroke patients. MATERIALS AND METHODS: 79 patients underwent 3.0 T MRI scans, including routine scans and MOLED technique. A deep learning network was utilized for image reconstruction, and the accuracy, reliability, and resistance to motion of the MOLED technique were validated on phantoms and volunteers. Subsequently, we assessed motor dysfunction severity, ischemic lesion volume, T2 values of the bilateral NA-CST, and the T2 ratio (rT2) between the ipsilesional and contralesional NA-CST in patients. RESULTS: The MOLED technique showed high accuracy (P < 0.001) and excellent repeatability, with a mean coefficient of variation (CoV) of 1.11%. It provided reliable quantitative results even under head movement, with a mean difference (Meandiff)= 0.28% and a standard deviation difference (SDdiff)= 1.34%. Additionally, the T2 value of the ipsilesional NA-CST was significantly higher than contralesional side (P < 0.001), and a positive correlation was observed between rT2 and the severity of motor dysfunction (rs =0.575, P < 0.001). Furthermore, rT2 successfully predicted post-stroke motor impairment, with an area under the curve (AUC) was 0.883. CONCLUSION: The MOLED technique offers significant advantages for quantitatively imaging stroke patients with involuntary movements. Additionally, T2 mapping from MOLED can detect microstructural changes in the NA-CST, potentially aiding in monitoring stroke-induced motor impairment.
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Imagen por Resonancia Magnética , Tractos Piramidales , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Persona de Mediana Edad , Tractos Piramidales/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/complicaciones , Imagen por Resonancia Magnética/métodos , Anciano , Reproducibilidad de los Resultados , Enfermedad Crónica , Adulto , Movimiento (Física) , Fantasmas de Imagen , Aprendizaje ProfundoRESUMEN
BACKGROUND: In the effort to prevent and control HIV/AIDS, China has established a national sentinel surveillance system. However, some sentinel sites face limitations in environmental resources and accessibility, prompting the exploration of alternative sample strategies. Dried plasma spots (DPS) samples are viewed as promising alternatives to traditional plasma samples due to their advantages, including sample stability, easy storage, and convenient transport. This study aims to develop a method for screening HIV, Treponema pallidum (TP), and Hepatitis C Virus (HCV) using DPS samples and assess their performance. METHODS: Based on existing commercial assay kits, a detection method was established through the optimization of experimental parameters, including the amount of plasma on filter paper, the volume of elution solution applied to dried plasma spots, the size of dried plasma spots, elution solution volume, elution solution components, elution temperature, and elution time. A series of laboratory evaluation panels were constructed for laboratory assessments, including the laboratory basic panel, laboratory interference panel, and laboratory precision panel. Additionally, clinical samples were used for evaluation. RESULTS: Optimal conditions for DPS sample extraction were: plasma volume, 100 µL; DPS size, whole spot; eluent volume, 500 µL; eluent, PBS with 1 Tween20; elution time, 2 h; elution temperature, room temperature. A total of 619 paired plasma/DPS samples were tested by both methods. The DPS-based ELISA method exhibited 100% sensitivity/specificity for HIV, 98.6%/100% for TP, and 99.6%/100% for HCV. Kappa values between the plasma samples and DPS samples were 100% for HIV, 99% for TP, and 100% for HCV. The DPS-based ELISA method failed to detect 1 HCV mono-infected sample and TP in 1 HIV/HCV/TP co-infected sample. For the HIV/HCV/TP co-infected sample, the S/CO in the plasma sample was 2.143 and in the DPS sample was 0.5. For HCV, the S/CO (sample OD/cut-off) was 3.049 in the plasma sample and 0.878 in the DPS sample. CONCLUSIONS: A single DPS, following one-time standardized processing, can be used to detect HIV, HCV, and TP. Researching and establishing laboratory testing methods better suited for China's sentinel surveillance have significant practical applications in improving HIV testing in resource-constrained environments.
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Infecciones por VIH , Hepatitis C , Sífilis , Humanos , Hepacivirus , Sífilis/diagnóstico , Hepatitis C/epidemiología , Plasma , Sensibilidad y Especificidad , Pruebas con Sangre Seca/métodosRESUMEN
Nuclear receptor subfamily 1, group D, member 1 (NR1D1, also known as REV-ERBα) belongs to the nuclear receptor (NR) family, and is a heme-binding component of the circadian clock that consolidates circadian oscillators. In addition to repressing the transcription of multiple clock genes associated with circadian rhythms, NR1D1 has a wide range of downstream target genes that are intimately involved in many physiopathological processes, including autophagy, immunity, inflammation, metabolism and aging in multiple organs. This review focuses on the pivotal role of NR1D1 as a key transcription factor in the gene regulatory network, with particular emphasis on the milestones of the latest discoveries of NR1D1 ligands. NR1D1 is considered as a promising drug target for treating diverse diseases and may contribute to research on innovative biomarkers and therapeutic targets for organ injury-related diseases. Further research on NR1D1 ligands in prospective human trials may pave the way for their clinical application in many organ injury-related disorders.
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Ritmo Circadiano , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares , Humanos , Estudios Prospectivos , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/genética , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/metabolismoRESUMEN
Nuclear medicine plays an irreplaceable role in the diagnosis and treatment of tumors. Radiopharmaceuticals are important components of nuclear medicine. Among the radiopharmaceuticals approved by the Food and Drug Administration (FDA), radio-tracers targeting prostate-specific membrane antigen (PSMA) and somatostatin receptor (SSTR) have held essential positions in the diagnosis and treatment of prostate cancers and neuroendocrine neoplasms, respectively. In recent years, FDA-approved serials of immune-therapy and targeted therapy drugs targeting programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), and nectin cell adhesion molecule 4 (Nectin 4). How to screen patients suitable for these treatments and monitor the therapy? Nuclear medicine with specific radiopharmaceuticals can visualize the expression level of those targets in systemic lesions and evaluate the efficacy of treatment. In addition to radiopharmaceuticals, imaging equipment is also a key step for nuclear medicine. Advanced equipment including total-body positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI) has been developed, which contribute to the diagnosis and treatment of tumors, as well as the development of new radiopharmaceuticals. Here, we conclude most recently advances of radiopharmaceuticals in nuclear medicine, and they substantially increase the "arsenal" of clinicians for tumor therapy.
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OBJECTIVES: The aim of this study was to design a novel tracer targeting programmed cell death-ligand 2 (PD-L2) to dynamically monitor PD-L2 expression and perform preclinical screening to identify patients who may benefit from immune checkpoint inhibitor therapy (ICI) therapy. METHODS: 89Zr labelling of DFO-conjugated PD-L2 antibody (ATL2) was carried out in Na2CO3 buffer at pH 7 (37 °C, 1 h). In vitro stability was analysed using radio-thin layer chromatography (radio-TLC). The affinity of [89Zr]Zr-DFO-ATL2 was evaluated by radio-ELISA. Cell uptake, pharmacokinetic, and biodistribution experiments were used to evaluate the biological properties. Micro-PET/CT imaging with [89Zr]Zr-DFO-ATL2 was conducted at different time points. Immunohistochemical and HE staining studies were carried out using tumour tissues from tumour-bearing mice. RESULTS: The radiochemical yield of [89Zr]Zr-DFO-ATL2 was 65.6 ± 3.9%, and the radiochemical purity (RCP) of the tracer was greater than 99%. The tracer maintained relatively high stability and had a high affinity for the PD-L2 protein (Kd = 31.85 nM, R2 = 0.94). The uptake of [89Zr]Zr-DFO-ATL2 in A549-PD-L2 cells was higher than that in A549 cells at each time point. Micro-PET/CT showed significant uptake in the tumour region of mice bearing tumours derived from A549-PD-L2 (SUVmax = 3.53 ± 0.09 at 96 h) and H2228 (SUVmax = 2.30 ± 0.12 at 48 h) cells. CONCLUSION: The high tumour uptake at early imaging time points demonstrates the feasibility of applying [89Zr]Zr-DFO-ATL2 to image PD-L2 expression in tumours and is encouraging for further clinical application in the screening of patients who may benefit from ICI therapy.
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Anticuerpos Monoclonales , Neoplasias Pulmonares , Humanos , Animales , Ratones , Anticuerpos Monoclonales/química , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Distribución Tisular , Deferoxamina , Línea Celular TumoralRESUMEN
Background: The effects of cannulated screws made of polyetheretherketone (PEEK) on the biomechanical properties of the vertebral body during vertebra-pediculoplasty remain unclear. This study aimed to investigate whether PEEK screws have the potential to replace titanium alloy screws. Methods: The surgical model of two different materials of screws was constructed using the finite element method. The biomechanical effects of the two models on the vertebral body under different working conditions were compared. Results: â The peak von Mises stress of PEEK screws was significantly lower than that of titanium screws, with a reduction ranging from 52% to 80%. â¡ The von Mises stress values for the injured T12 spine were similar for both materials. Additionally, the segmental range of motion and intervertebral disc pressure showed no significant difference between the two materials. Conclusion: PEEK screws demonstrated advantages over titanium screws and may serve as a viable alternative for screw materials in vertebra-pediculoplasty.
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BACKGROUND: In this study, we compared the prognosis, tumor immune microenvironment (TIM), and drug treatment response between left-sided (LCC) and right-sided (RCC) colon cancer to predict outcomes in patients with LCC and RCC. METHODS: Based on identified differentially expressed genes and using single-cell RNA sequencing data, we constructed and validated a prognostic model for LCC and RCC patients in the TCGA-COAD cohort and GSE103479 cohort. Moreover, we compared the differences of TIM characteristics and drug treatment response between LCC and RCC patients. RESULTS: We constructed and validated a five-gene prognostic model for LCC patients and a four-gene prognostic model for RCC patients, and both showed excellent performance. The RCC patients with higher risk scores were significantly associated with greater metastasis (P = 2.6×10-5), N stage (P = 0.012), advanced pathological stage (P = 1.4×10-4), and more stable microsatellite status (P = 0.007) but not T stage (P = 0.200). For LCC patients, the risk scores were not significantly associated with tumor stage and microsatellite status (P > 0.05). Additionally, immune infiltration by CD8 and regulatory T cells and M0, M1, and M2 macrophages differed significantly between LCC and RCC patients (P < 0.05). APC and TP53 mutations were significantly more common in LCC patients (P < 0.05). In contrast, KRAS, SYNE1, and MUC16 mutations were significantly more common in RCC patients (P < 0.05). In addition, tumor mutation burden values were significantly higher in RCC patients than in LCC patients (P = 5.9×10-8). Moreover, the expression of immune checkpoint targets was significantly higher in RCC patients than in LCC patients (P < 0.05), indicating that RCC patients maybe more sensitive to immunotherapy. However, LCC and RCC patients did not differ significantly in their sensitivity to eight selected chemicals or target drugs (P > 0.05). The average half-maximal inhibitory concentrations for camptothecin, teniposide, vinorelbine, and mitoxantrone were significantly lower in low-risk than in high-risk RCC patients (P < 0.05), indicating that the lower risk score of RCC patients, the more sensitive they were to these four drugs. CONCLUSIONS: We investigated the differences in prognosis, TIM, and drug treatment response between LCC and RCC patients, which may contribute to accurate colon cancer prognosis and treatment of colon cancer.
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Carcinoma de Células Renales , Neoplasias del Colon , Neoplasias Renales , Humanos , RNA-Seq , Análisis de Expresión Génica de una Sola Célula , Pronóstico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: To assess the image quality feasibility and diagnostic value of zoomed diffusion-weighted imaging (z-EPI DWI) using echo-planar imaging (EPI) compared with conventional DWI (c-EPI DWI) in patients with periampullary disease. METHODS: Thirty-six patients with periampullary carcinomas and fifteen with benign periampullary disease were included in this study. All the subjects underwent MR cholangiopancreatography (MRCP), c-EPI DWI, and z-EPI DWI. Two radiologists independently assessed image quality of the two image sets, including overall image quality and lesion conspicuity. In addition, signal intensity and ADC measurements of DWIs in the periampullary lesions were conducted. Diagnostic accuracies of the combined image sets of MRCP and z-EPI DWI were compared with those of a combined set of MRCP and c-EPI DWI. RESULTS: z-EPI DWI showed significantly better image quality scores (anatomic structure visualization, 2.94 ± 0.24; overall image quality, 2.96 ± 0.17) compared to that with c-EPI DWI (anatomic structure visualization, 2.02 ± 0.22; overall image quality, 2.04 ± 0.24) (both P < 0.01). For all the periampullary malignant lesions and small lesions (≤ 20 mm), there was better delineation of lesion conspicuity and the lesion margin, as well as diagnostic confidence with z-EPI DWI (all P < 0.05). The rate of periampullary malignancy's hyperintense signal on z-EPI DWI was increased to 91.7% (33/36) compared to c-EPI DWI (69.4% (25/36)) (P = 0.023). For all malignant lesions and small lesions, the diagnostic accuracy scores were increased using the MRCP and z-EPI DWI combined set, compared to the MRCP and c-EPI DWI combined set (P < 0.05). Diagnostic accuracy for detection and differentiation of malignant lesions from benign lesions significantly improved for the MRCP and z-EPI DWI combined set compared with MRCP and c-EPI DWI combined set (P < 0.05). There were no significant differences between c-EPI DWI and z-EPI DWI in the ADC values of periampullary malignant and benign lesions (P > 0.05). CONCLUSIONS: z-EPI DWI has an advantage that could lead to remarkable image quality improvements and enhanced lesion visualization of periampullary carcinomas. z-EPI DWI was superior to c-EPI DWI for detecting, delineating, and diagnosing the lesions, particularly for small challenging lesions.