Theranostics最新文献

{"title":"Towards practical radiopharmaceutical treatment planning: a review of dosimetry simplification techniques.","authors":"Elmira Yazdani, Zahra Mansouri, Yazdan Salimi, Habib Zaidi","doi":"10.7150/thno.132538","DOIUrl":"10.7150/thno.132538","url":null,"abstract":"<p><p>Radiopharmaceutical therapy (RPT) plays an important role in modern precision oncology. However, treatment activity is still prescribed by fixed-dose protocols rather than adjusted to planned patient-specific absorbed dose (AD). Individualized dosimetry holds promise for improving treatment planning but is not yet standard. One main reason is that present dosimetry workflows depend on repeated imaging at multiple time points and require kinetic modeling and computational modeling. This review covers recent approaches to make dosimetry more practical and easier to use in everyday RPT workflows. We introduce a theoretical framework in which simplification methods, which help ease the clinical burden of dosimetry, are classified into three related categories. The first two categories simplify the process through direct reduction in the burdens of either the acquisition or processing of data: (1) Methodological simplifications through reduction in the imaging burden, such as reduced- or single-time point (STP) imaging; and (2) Computational automation via artificial intelligence (AI) to automate dosimetry, including image processing, segmentation, registration, and AD estimation. Advanced modeling strategies in the third category improve efficiency through inference, thereby enabling estimation of AD from sparsely sampled data. Reduced imaging played a major role in defining these areas. While all of these have their promise, every category of methods has certain drawbacks. STP techniques are less reliable for heterogeneous tumors, black box models have poor transferability and explainability, and digital twin/physiologically-based pharmacokinetic (DT/PBPK) models lack clinical validation. Fundamental dosimetry, with appropriate validity conditions, could allow for reduced reliance on imaging skills and expertise while still retaining sufficient precision for its intended purposes. Standardization of imaging and multicenter analysis is essential for wider adoption of RPTs. A detailed description of models and their effectiveness would be helpful in the clinical application of dosimetry.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 15","pages":"8775-8807"},"PeriodicalIF":14.9,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbial enzyme-responsive inulin nanoparticles for colon-targeted oral delivery of 5-ASA toward improved therapy of inflammatory bowel disease.","authors":"Haena Park, Panmo Son, Chiwoo Oh, Hyeryeon Oh, Jee-Eun Hwang, Seo Young Kim, Jeongcheol Lee, Jae Kyoo Lee, Won Il Choi, Hyung-Jun Im","doi":"10.7150/thno.127560","DOIUrl":"10.7150/thno.127560","url":null,"abstract":"<p><p>Colon-targeted delivery of 5-aminosalicylic acid (5-ASA) offers an effective strategy for treating inflammatory bowel disease (IBD) while minimizing systemic side effects. However, conventional oral 5-ASA formulations suffer from premature drug release and poor colon specificity. To overcome these limitations, we developed a biodegradable, prebiotic, and immunomodulatory inulin nanoparticle (INP) platform enabling microbial enzyme-responsive and site-specific release of 5-ASA in the colon.</p><p><strong>Methods: </strong>INP was fabricated via a mild nanoprecipitation method and loaded with 5-ASA (5-ASA@INP). Physicochemical characteristics, drug-loading performance, and enzyme-responsive sequential release profiles under simulated gastrointestinal fluids were evaluated. Antioxidant and anti-inflammatory effects were assessed <i>in vitro</i>. Biodistribution of DiR-labeled INPs was analyzed to demonstrate colon-targeting efficacy. Therapeutic efficacy, inflammatory cytokine expression, Treg responses in the colon and gut-associated lymphoid tissues, and microbiota-related effects, including short-chain fatty acid (SCFA) production, were evaluated in a colitis mouse model.</p><p><strong>Results: </strong>5-ASA@INP showed 97.02% drug-loading efficiency. The cumulative release of 5-ASA was 7.6% in simulated gastric fluid, 18.7% in simulated intestinal fluid, and 99.2% in simulated colonic fluid. In contrast, only 35.6% of 5-ASA was released under enzyme-free simulated colonic conditions. Compared with free 5-ASA, 5-ASA@INP showed enhanced antioxidant and anti-inflammatory effects <i>in vitro</i>. <i>In vivo</i>, INPs preferentially accumulated in the colon with minimal off-target distribution. In colitic mice, 5-ASA@INP significantly attenuated body weight loss (<i>p</i> = 0.0067) and colon shortening (<i>p</i> = 0.0002). Histological analysis showed that the colonic tissue damage was minimized and the inflammation scores were reduced (<i>p</i> < 0.001). Treatment increased the number of FOXP3+ cells in the colonic tissue and suppressed the expression of IL-17A, TNF-α, and IL-1β. The gut microbial profile was restored toward that of the normal group and fecal SCFA levels were increased.</p><p><strong>Conclusions: </strong>This study demonstrates that the INP platform enables microbial enzyme-responsive, colon-targeted delivery of 5-ASA while complementarily harnessing the intrinsic prebiotic and immunomodulatory properties of inulin. This dual-function nanoplatform provides a promising strategy for efficient oral treatment of IBD.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 15","pages":"8892-8913"},"PeriodicalIF":14.9,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered nanomedicine remodels the postoperative cavity microenvironment to suppress glioblastoma recurrence.","authors":"Zhiqun Bai, Zhiguang Chen","doi":"10.7150/thno.141774","DOIUrl":"10.7150/thno.141774","url":null,"abstract":"<p><p>Glioblastoma (GBM) has a high rate of post-surgical recurrence, which can be attributed to residual tumor cells as well as to the disruption of the tumor microenvironment (TME) caused by surgery. Here, we define the postoperative cavity microenvironment (POCM) as a pathological niche with distinct spatial and temporal boundaries, and present a list of markers that outline this environment, including low pH, high levels of reactive oxygen species (ROS), high levels of glutathione (GSH), overexpression of matrix metalloproteinases, and tumor tissue mechanical instability. Engineered nanomedicine is evolving from simple drug-carrying entities to the design of smart responsive materials that can be actively tuned to modulate the POCM. In this review, we outline the working mechanisms and main features of different classes of smart responsive materials, which not only release therapeutic agents but also provide spatiotemporal control over drug delivery, enhance penetration into residual tumor tissue, and trigger immune activation at the right time and place. We discuss how local delivery of nanogel-based platforms in combination with systemic immunotherapy and fine-tuning by means of 3D bioprinting and/or microfluidic chip-based platforms can provide effective tools for reducing post-operative GBM recurrence rates.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 15","pages":"8914-8946"},"PeriodicalIF":14.9,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted phagocytosis of TNF-α by CAR macrophages restores immune homeostasis in arthritis.","authors":"Mei-Qi Wang, Jie Zhu, Chun-Yu Liu, Xiao-Lin Yu, Ya-Ru Huang, Lei Zhang, Shi-Yu Liang, Lixia Zhang, Hao-Tian Wang, Hongbo Cheng, Jia-Qian Chai, Xi-Xiu Xie, Rui-Tian Liu","doi":"10.7150/thno.132172","DOIUrl":"10.7150/thno.132172","url":null,"abstract":"<p><strong>Rationale: </strong>Dysregulated phagocytic clearance within the synovial microenvironment contributes to persistent inflammation and impairs immune homeostasis in rheumatoid arthritis (RA). Because MerTK-positive macrophages are essential for efferocytosis and inflammation resolution, but are functionally impaired in RA, this study aimed to engineer macrophages capable of enhancing tumor necrosis factor-α (TNF-α) clearance and restoring inflammation-resolving macrophage function.</p><p><strong>Methods: </strong>We generated anti-TNFα chimeric antigen receptor macrophages (CAR-M) by replacing the MerTK antigen-binding domain with a TNF-R1 fragment. The phagocytic and degradative capacity of CAR-M toward soluble TNF-α was assessed, together with activation of Rho GTPases Rac1, Cdc42, and RhoA. Macrophage inflammatory mediator production, phenotypic polarization, SOCS1/3, NF-κB, and MAPK signaling were analyzed. The effects of CAR-M cells were further compared with adalimumab and control treatments under synovial fluid stimulation from patients with arthritis and in mice with collagen-induced arthritis (CIA).</p><p><strong>Results: </strong>Anti-TNFα CAR-M showed markedly enhanced phagocytosis and degradation of soluble TNF-α, accompanied by Rac1, Cdc42, and RhoA activation. CAR activation reduced inflammatory mediator production, including soluble TNF-α, interleukin-1 β (IL-1β), and interleukin-6 (IL-6), while increasing interleukin-10 (IL-10) secretion. This functional shift was associated with polarization toward an inflammation-resolving MerTK⁺CD206⁺ phenotype, SOCS1/3 upregulation, and NF-κB and MAPK pathway inhibition. Under stimulation with synovial fluid from arthritis patients, anti-TNFα CAR-M decreased TNF-α and IL-6 levels and drove macrophages toward an M2-like anti-inflammatory state. In CIA mice, local <i>in situ</i> CAR-M cell treatment produced stronger therapeutic effects than adalimumab or other controls, significantly alleviating inflammatory activation, clinical symptoms, and joint pathologies.</p><p><strong>Conclusions: </strong>Anti-TNFα CAR-M exert therapeutic effects via a dual mechanism: direct TNF-α clearance and synovial macrophage reprogramming toward a reparative phenotype. This synthetic biology strategy highlights the potential of precise cell engineering to correct phagocytic deficits and resolve chronic inflammation in RA.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 15","pages":"9007-9029"},"PeriodicalIF":14.9,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EBDE clearing: A strategy for simultaneous 3D visualization and quantitative analysis of both renal arteries and glomeruli.","authors":"Yaping Wu, Qian Shen, Yan Liang, Lin Bai, Jinsai Wu, Qiuxiao Shi, Lei Wu, Menqi Wang, Yin Liu, Kui Huang","doi":"10.7150/thno.138951","DOIUrl":"10.7150/thno.138951","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Three-dimensional (3D) visualization of the renal vasculature plays a crucial role in the pathological assessment and mechanistic investigation of kidney diseases. However, existing 3D imaging approaches remain unable to rapidly and accurately achieve continuous visualization spanning from millimeter-scale arteries to micrometer-scale glomerular capillaries. Here, we developed an innovative strategy, termed EBDE clearing, which enables continuous 3D visualization from the renal artery to the glomerulus, systematically characterizes the spatiotemporal architecture of the entire renal arterial tree and glomeruli in unilateral ureteral obstruction (UUO) and diabetic nephropathy (DN) mouse models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We combined the vascular tracers of Evans blue and dextran with Ethanol-ECi tissue clearing (EBDE clearing) to achieve the improved labeling of all renal arteries and glomeruli. By further integrating light-sheet microscopy-based 3D imaging with reconstruction and segmentation, we performed high-resolution 3D visualization and quantitative analysis of both renal vascular and glomeruli in normal and diseased kidneys. Furthermore, we investigated, classified, and statistically analyzed the spatiotemporal architecture of the arteries and glomeruli in the kidneys of mice with UUO and DN.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Firstly, through quantitative analysis of renal artery diameter, vascular branching, and vascular segment straightness, we found that the arteries of both UUO and DN mice exhibited varying degrees of damage. The renal vascular damage in UUO mice was more severe, manifested by a significant reduction in vessel diameter and the number of vascular branches, as well as an increased in the segment straightness of some arteries; in contrast, the pathological changes in the renal arteries of DN mice were mainly concentrated in vessel diameter and the number of vascular branches. We further classified the glomeruli into three distinct types (M1, M2, and M3) based on their origins, and conducted a quantitative analysis of their 3D spatial distribution within the kidneys of UUO and DN mice, and discovered that in UUO mice, there was a severe reduction in the number and the average volume of the both total and the individual M1-M3 glomeruli. However, in the DN mice, apart from no changes in the total and M1 glomerular number, the other relevant pathological parameters of glomeruli also showed a decrease, although the extent of this decrease was much milder compared to that in the UUO mice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;EBDE clearing enables continuous, high-resolution 3D visualization and quantitative analysis from the renal artery to the glomerulus in both normal and diseased intact kidneys. The study not only provides important insights into the renal pathophysiology of UUO and DN, but also establishes a rapid and comprehensive strategy for visualizing structural alterations during disea","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 15","pages":"8987-9006"},"PeriodicalIF":14.9,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical efficacy and dosimetry of CD44v6-directed terbium-161 radionuclide therapy.","authors":"Amanda Gustafsson, Anja Charlotte Lundgren Mortensen, Veronica Rondahl, Tianqi Xu, Klas Bratteby, Peter Bernhardt, Marika Nestor","doi":"10.7150/thno.135243","DOIUrl":"10.7150/thno.135243","url":null,"abstract":"<p><strong>Rationale: </strong>Lutetium-177 has demonstrated clinical success, particularly in neuroendocrine and prostate cancers, but disease recurrence and progression remain frequent. Terbium-161 offers improved therapeutic potential by delivering higher localized radiation doses. We have previously demonstrated preclinical efficacy of the CD44v6-targeted radiopharmaceutical [¹⁷⁷Lu]Lu-AKIR001, which is currently under clinical investigation for multiple malignancies (NCT06639191). The present study explored the terbium-161-labeled analogue preclinically, focusing on pancreatic ductal adenocarcinoma, with early proof-of-concept investigations in squamous cell carcinoma, both being highly aggressive and treatment-resistant malignancies.</p><p><strong>Methods: </strong>Radioligand uptake was evaluated <i>in vitro</i> in squamous cell carcinoma and pancreatic ductal adenocarcinoma cell lines. <i>Ex vivo</i> biodistribution and dosimetry estimations confirmed a selective tumor uptake of [¹⁶¹Tb]Tb-AKIR001 before therapeutic efficacy was evaluated in both squamous cell carcinoma and pancreatic ductal adenocarcinoma xenograft models. Mice were administered [¹⁶¹Tb]Tb-AKIR001 of activities ranging from 4 to 10 MBq and compared to untreated controls. Potential adverse effects were evaluated by blood sampling, monitoring of body weights, and histopathology.</p><p><strong>Results: </strong>Specific, high-affinity binding of [¹⁶¹Tb]Tb-AKIR001 to CD44v6-positive cells was verified <i>in vitro</i>. Tumor uptake <i>in vivo</i> exceeded 30% injected activity per gram of tissue in the A431 model at 96 h post-injection. Peak tumor uptake in the BxPC3 model exceeded 150% injected activity per gram of tissue, with a mean absorbed dose to tumor of 17 Gy/MBq. Activity-dependent antitumor effects were observed in both xenograft models, accompanied by mild to moderate, transient hematologic effects that were significantly mitigated by activity fractionation. Histopathological evaluation revealed no treatment-related tissue damage in kidney, liver or spleen.</p><p><strong>Conclusion: </strong>[¹⁶¹Tb]Tb-AKIR001 demonstrated favorable biodistribution and dosimetry profiles, together with encouraging therapeutic effects without signs of severe toxicity. Compared to [¹⁷⁷Lu]Lu-AKIR001, [¹⁶¹Tb]Tb-AKIR001 may offer added advantages in certain therapeutic contexts, and our results highlight [¹⁶¹Tb]Tb-AKIR001 as a promising candidate for further development in targeted radionuclide therapy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 15","pages":"8880-8891"},"PeriodicalIF":14.9,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colon-targeted oral delivery of melatonin for regulating macrophage activity and intestinal barrier in ulcerative colitis.","authors":"Nhu-Nam Nguyen, Yoojin Seo, Tiep Tien Nguyen, Kim-Phuong Phan, Rabyya Kausar, Hu-Lin Jiang, Jae Young Lee, Seho Kweon, Nguyen-Thach Tung, Hyung-Sik Kim, Jee-Heon Jeong","doi":"10.7150/thno.133456","DOIUrl":"10.7150/thno.133456","url":null,"abstract":"<p><strong>Background: </strong>Despite its promising therapeutic potential, inefficient site-specific targeting and complex fabrication processes hinder the clinical translation of oral melatonin therapy for ulcerative colitis (UC). Herein, we present <b>M</b>elatonin-<b>E</b>udragit-<b>T</b>hioketal polymer-based <b>A</b>ssembly (<b>META</b>), a dual pH/ROS-responsive oral microsphere for precise melatonin delivery to the inflamed colon and enhanced therapeutic outcomes.</p><p><strong>Methods: </strong>META was fabricated via a scalable emulsification process using Eudragit^® FS 30 D and a thioketal polymer to enable dual pH- and ROS-responsive release. Its targeting delivery and therapeutic effects were then evaluated in simulated gastrointestinal (GI) fluids, 2D cell models, intestinal organoids, and a murine colitis model.</p><p><strong>Results: </strong>Using cell and animal models, we showed the important role of melatonin in GI health, supporting our strategy for UC treatment. META exhibited controlled melatonin release and better accumulation in the inflamed colon. The targeted delivery helped promote disease recovery by modulating macrophages and improving the intestinal barrier.</p><p><strong>Conclusion: </strong>META delivers melatonin precisely to the colon, which reprograms colonic macrophages and reinforces the epithelial barrier. This study offers a practical, clinically relevant approach for improving the use of endogenous therapeutic molecules in UC and other inflammatory GI diseases.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 15","pages":"8860-8879"},"PeriodicalIF":14.9,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feedback-regulated 3D-printed hydrogel micropatch for integrated therapy of fungal keratitis.","authors":"Yujie Liu, Li Ma, Guodong Fang, Tan Li, Hongran Zhao, Ting Wu, Jiajia Zhang, Xia Qi, Xiangyue Hu, Hongwei Wang, Chao Yang, Depeng Shi","doi":"10.7150/thno.134232","DOIUrl":"10.7150/thno.134232","url":null,"abstract":"<p><strong>Rationale: </strong>Fungal keratitis remains clinically challenging due to limited drug bioavailability, frequent dosing, reactive oxygen species (ROS)-mediated stromal damage, perforation risk, and bacterial coinfection. In the study, we developed a feedback-regulated multifunctional corneal micropatch (MFCP) via 3D printing for the treatment of fungal keratitis.</p><p><strong>Methods: </strong>The dual-network hydrogel micropatch comprises an ROS-responsive hydrogel (RRH), voriconazole-loaded F127DA micelles (VCZ-F127DA), and gatifloxacin-loaded cerium metal-organic frameworks (GAT-MOFs). We characterized its physicochemical properties and evaluated its biocompatibility, corneal healing capacity, ROS scavenging activity, and antimicrobial performance. Histological staining, cytokine assays, and transcriptomic sequencing were used to assess its therapeutic efficacy in a mouse model of fungal keratitis.</p><p><strong>Results: </strong>MFCP exhibits tunable curvature, high transparency, and mechanical properties matching those of the cornea, along with good biocompatibility. High ROS level can accelerate breakdown of the micropatch and promote drug release, generating strong synergistic antifungal and antibacterial activities. The released GAT-MOFs scavenge excessive ROS, forming a negative feedback loop. In the mouse model of fungal keratitis, MFCP mitigates corneal infection, lowers proinflammatory cytokines, and accelerates tissue repair, with therapeutic efficacy superior to that of voriconazole eye drops. Transcriptomic analysis reveals suppression of NF-κB-mediated inflammatory signaling and upregulation of corneal regenerative pathways after treatment with MFCP.</p><p><strong>Conclusion: </strong>These findings demonstrate that MFCP represents a viable therapeutic option for fungal keratitis.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 15","pages":"8827-8843"},"PeriodicalIF":14.9,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D vascular mapping reveals multi-organ injury following severe acute pancreatitis.","authors":"Xiaomei Liu, Jingtan Zhu, Qiao Shi, Jianyi Xu, Zhang Liu, Yujia Kang, Kunxing Liu, Yuening He, Qihang Yang, Tingting Yu, Dan Zhu","doi":"10.7150/thno.141299","DOIUrl":"10.7150/thno.141299","url":null,"abstract":"<p><strong>Rationale: </strong>Severe acute pancreatitis (SAP) is a life-threatening disease with substantial mortality, primarily resulting from pancreatic microcirculatory failure that initiates multiple organ dysfunction syndrome (MODS). While early microvascular injury is widely recognized as a critical determinant of disease progression, the precise spatiotemporal dynamics and mechanisms underlying vascular damage remain largely elusive, limiting the development of effective therapeutic interventions.</p><p><strong>Methods: </strong>An integrated imaging method that combines vascular labeling, tissue clearing, and light-sheet microscopy is proposed to realize 3D mapping and quantitative analysis of multi-organ vascular networks in a mouse model of SAP.</p><p><strong>Results: </strong>We found that SAP induced systemic microvascular disruption accompanied by organ-specific perfusion deficits across multiple vital organs. As the primary site of injury, the pancreas exhibited the earliest and most severe hypoperfusion, whereas remote organs showed a delayed decline in perfusion, with different trends among organs. Specifically, perfusion in the lung, heart, and kidney decreased gradually with disease progression, perfusion in the liver and spleen remained stable within the first 6 hours and then decreased rapidly, while the brain perfusion showed a sharp decrease at the end stage. These distinct perfusion trajectories are consistent with sequential compensatory and decompensatory responses. More importantly, the administration of heparin sodium within 12 hours after SAP induction significantly improved survival, reversed multi-organ hypoperfusion, and preserved microvascular integrity across affected organs.</p><p><strong>Conclusions: </strong>This study identifies systemic vascular injury as a key driver of multiple organ dysfunction in SAP and provides a convincing evidence that early intervention with heparin sodium can improve multi-organ hypoperfusion, preserve microvascular integrity, and enhance survival.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 15","pages":"8844-8859"},"PeriodicalIF":14.9,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"hNET-targeted [¹⁸F]MFBG PET as baseline functional imaging in newly diagnosed neuroblastoma.","authors":"Lifeng Zhang, Xinhui Su, Xinyue Zheng, En Ren, Li Hou, Junqing Mao, Tingting Zhang, Jinhu Wang, Jingjing Zhang, Peipei Wang","doi":"10.7150/thno.139324","DOIUrl":"10.7150/thno.139324","url":null,"abstract":"<p><strong>Rationale: </strong>[¹⁸F]meta-fluorobenzylguanidine ([¹⁸F]MFBG) is an human norepinephrine transporter (hNET)-targeted PET tracer that has shown superior lesion detection than [¹²³I]MIBG SPECT in patients with relapsed or refractory neuroblastoma. Its value in newly diagnosed patients, however, has not been well established. We therefore performed this study to evaluate the additional staging information of [¹⁸F]MFBG beyond comprehensive anatomic imaging and assessed its agreement with [¹⁸F]FDG PET at baseline.</p><p><strong>Methods: </strong>We prospectively enrolled consecutive children with newly diagnosed neuroblastoma. All patients underwent baseline [¹⁸F]MFBG PET and comprehensive anatomic imaging, including contrast-enhanced CT and/ or MRI from the neck to the pelvis and whole-body ultrasonography. The imaging studies were interpreted independently, and lesion distribution and International Neuroblastoma Risk Classification (INRG) stage were recorded. A subgroup also underwent paired [¹⁸F]FDG PET for functional comparison. Paired detection rates were compared using the McNemar test. Intermodality concordance was evaluated using Cohen κ statistics, and Curie scores were compared using Wilcoxon signed-rank tests.</p><p><strong>Results: </strong>Forty patients (median age, 23.5 months) were analyzed. The primary tumors were mainly located in the abdomen or pelvis (36/40, 90%), with corresponding imaging findings including contrast-enhanced abdominopelvic CT and MRI, non-contrast cervicothoracic CT, and whole-body ultrasonography. [¹⁸F]MFBG PET identified bone marrow metastases more frequently than anatomic imaging (65% vs. 32.5%, P = 0.001; κ = 0.41), leading to stage reclassification in 20% of cases and treatment modification in 10% based on tumor-board review. Even within overlapping fields of view (neck to proximal femur), [¹⁸F]MFBG maintained superior bone marrow detection rates (55% vs. 32.5%, P = 0.004; κ = 0.56). Among the patients initially classified as L2, half were upstaged based on hNET-targeted PET findings. In the paired [¹⁸F]FDG PET subset (n = 26), the patient-level INRG stage was fully concordant between modalities. However, lesion-level analysis revealed a higher bone marrow disease burden on [¹⁸F]MFBG (191 vs. 140, P = 0.002), while FDG detected 13% additional nodal lesions in five patients.</p><p><strong>Conclusion: </strong>In newly diagnosed neuroblastoma, hNET-targeted [¹⁸F]MFBG PET detected clinically relevant bone marrow involvement not identified by comprehensive anatomic imaging, resulting in stage reclassification and treatment modification in a subset of patients. Paired [¹⁸F]FDG PET demonstrated patient-level stage concordance with lesion-level heterogeneity.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 15","pages":"9030-9040"},"PeriodicalIF":14.9,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}