{"title":"Prospective Clinical Assessment of Ultrasound-Assisted Radiopharmaceutical Imaging Under Anesthesia for Oncologic Evaluation.","authors":"Qinghua Meng, Li Lin, Rongzhu Lei","doi":"10.1177/10849785261432906","DOIUrl":"10.1177/10849785261432906","url":null,"abstract":"<p><strong>Background: </strong>Ultrasound (US) is widely used in oncology, yet prospective clinical evidence for integrating US into radiopharmaceutical positron emission tomography/computed tomography (PET/CT) workflows remains limited. We assessed whether a standardized periprocedural US step under anesthesia improves lesion detectability and quantitative conspicuity without compromising safety.</p><p><strong>Methods: </strong>In a prospective single-arm trial, 39 patients were enrolled and 38 completed US-assisted PET/CT. Under general anesthesia with continuous monitoring, US was applied to the target region immediately before radiotracer administration, followed by whole-body PET/CT under uninterrupted anesthesia. Two blinded nuclear medicine physicians interpreted paired standard versus US-assisted datasets, scoring lesion detection and 5-point confidence. Primary endpoints were within-patient change in detection and confidence. Secondary endpoints included standardized uptake value/tumor-to-background ratio (TBR) metrics, management change, and Common Terminology Criteria for Adverse Events (CTCAE)-graded safety. Paired McNemar and Wilcoxon signed-rank tests were used; κ quantified interreader agreement.</p><p><strong>Results: </strong>US assistance increased lesion detection and improved reader confidence, with higher paired TBR and most patients showing clinically meaningful TBR gains. Management changed in 12/38 (31.6%). No CTCAE grade ≥3 events occurred; vitals remained stable, and stop criteria were not triggered.</p><p><strong>Conclusions: </strong>US integration into PET/CT under anesthesia was feasible and safe, improving imaging performance and clinical decision impact, aligning with clinical trial and risk-focused US oncology priorities.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"469-480"},"PeriodicalIF":1.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuran Huo, Wuwen Zhang, Yingnan Wang, Jing Qi, Yang Wang, Chunying Bai
{"title":"Deep Learning Integration of Endoscopic Ultrasound Features and Serum Data Reveals <i>LTB4</i> as a Diagnostic and Therapeutic Target in esophageal squamous cell carcinoma.","authors":"Shuran Huo, Wuwen Zhang, Yingnan Wang, Jing Qi, Yang Wang, Chunying Bai","doi":"10.1177/10849785251380368","DOIUrl":"10.1177/10849785251380368","url":null,"abstract":"<p><strong>Background: </strong>Early diagnosis and accurate prediction of treatment response in esophageal squamous cell carcinoma (ESCC) remain major clinical challenges due to the lack of reliable and noninvasive biomarkers. Recently, artificial intelligence-driven endoscopic ultrasound image analysis has shown great promise in revealing genomic features associated with imaging phenotypes.</p><p><strong>Methods: </strong>A prospective study of 115 patients with ESCC was conducted. Deep features were extracted from endoscopic ultrasound using a ResNet50 convolutional neural network. Important features shared across three machine learning models (NN, GLM, DT) were used to construct an image-derived signature. Plasma levels of leukotriene B4 (<i>LTB4</i>) and other inflammatory markers were measured using enzyme-linked immunosorbent assay. Correlations between signature and inflammation markers were analyzed, followed by logistic regression and subgroup analyses.</p><p><strong>Results: </strong>The endoscopic ultrasound image-derived signature, generated using deep learning algorithms, effectively distinguished esophageal cancer from normal esophageal tissue. Among all inflammatory markers, <i>LTB4</i> exhibited the strongest negative correlation with the image signature and showed significantly higher expression in the healthy control group. Multivariate logistic regression analysis identified <i>LTB4</i> as an independent risk factor for ESCC (odds ratio = 1.74, <i>p</i> = 0.037). Furthermore, <i>LTB4</i> expression was significantly associated with patient sex, age, and chemotherapy response. Notably, higher <i>LTB4</i> levels were linked to an increased likelihood of achieving a favorable therapeutic response.</p><p><strong>Conclusions: </strong>This study demonstrates that deep learning-derived endoscopic ultrasound image features can effectively distinguish ESCC from normal esophageal tissue. By integrating image features with serological data, the authors identified <i>LTB4</i> as a key inflammation-related biomarker with significant diagnostic and therapeutic predictive value.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"481-489"},"PeriodicalIF":1.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dawood Khan, Hafiz Zia Ur Rehman, Sara Ali, Hyunho Hwang, Kashif Anwar
{"title":"Neural Decoding of Ultrasound-Modulated Pain States via Deep Learning: Insights from Functional Magnetic Resonance Imaging Data.","authors":"Dawood Khan, Hafiz Zia Ur Rehman, Sara Ali, Hyunho Hwang, Kashif Anwar","doi":"10.1177/10849785251414768","DOIUrl":"10.1177/10849785251414768","url":null,"abstract":"<p><p>Focused ultrasound (FUS) is a noninvasive neuromodulation technique capable of modulating deep-brain circuits with millimeter precision. When combined with functional magnetic resonance imaging (fMRI), it enables causal decoding of brain-state dynamics <i>in vivo</i>. In this study, the authors applied deep learning to fMRI data acquired from nonhuman primates during thermal pain stimulation with and without transcranial FUS targeting the ventral posterolateral (VPL) nucleus of the thalamus, a key somatosensory relay. A 3D convolutional neural network was trained to classify three experimental conditions: Heat (pain only), Heat + FUS, and FUS-only. The model achieved an average accuracy of 92.2% (binary) and 91.2% (multiclass), with receiver operating characteristic-area under the curve values exceeding 0.90. Saliency mapping revealed significant cortical suppression in the secondary somatosensory cortex (S2, <i>p</i> = 0.036) and insula (<i>p</i> = 0.024), accompanied by preserved thalamic relevance in the VPL. In FUS-only trials, saliency shifted toward dorsolateral prefrontal regions, suggesting cognitive engagement even in the absence of nociceptive input. These findings demonstrate that FUS attenuates thalamocortical pain transmission while maintaining subcortical relay integrity. This work highlights the translational potential of FUS as a targeted, reversible neuromodulation strategy and underscores the value of artificial intelligence-driven neuroimaging in decoding dynamic pain states.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":"41 6","pages":"528-543"},"PeriodicalIF":1.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148406939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dual-Parallel Artificial Intelligence Framework for Breast Cancer Grading via High-Intensity Ultrasound and Biomarkers.","authors":"Pritee Parwekar, Krishna Kant Agrawal, Jabir Ali, Shilpa Gundagatti, Dharmveer Singh Rajpoot, Tanveer Ahmed, Ankit Vidyarthi","doi":"10.1177/10849785251383328","DOIUrl":"10.1177/10849785251383328","url":null,"abstract":"<p><strong>Background: </strong>Accurate and noninvasive breast cancer grading and therapy monitoring remain critical challenges in oncology. Traditional methods often rely on invasive histopathological assessments or imaging-only techniques, which may not fully capture the molecular and morphological intricacies of tumor response.</p><p><strong>Method: </strong>This article presents a novel, noninvasive framework for breast cancer analysis and therapy monitoring that combines two parallel mechanisms: (1) a dual-stream convolutional neural network (CNN) processing high-intensity ultrasound images, and (2) a biomarker-aware CNN stream utilizing patient-specific breast cancer biomarkers, including carbohydrate antigen 15-3, carcinoembryonic antigen, and human epidermal growth factor receptor 2 levels. The imaging stream extracts spatial and morphological features, while the biomarker stream encodes quantitative molecular indicators, enabling a multimodal understanding of tumor characteristics. The outputs from both streams are fused to predict the cancer grade (G1-G3) with high reliability.</p><p><strong>Results: </strong>Experimental evaluation on a cohort of pre- and postchemotherapy patients demonstrated the effectiveness of the proposed approach, achieving an overall grading accuracy of 97.8%, with an area under the curve of 0.981 for malignancy classification. The model also enables quantitative post-therapy analysis, revealing an average tumor response improvement of 41.3% across the test set, as measured by predicted regression in grade and changes in biomarker-imaging correlation.</p><p><strong>Conclusions: </strong>This dual-parallel artificial intelligence strategy offers a promising noninvasive alternative to traditional histopathological and imaging-alone methods, supporting real-time cancer monitoring and personalized treatment evaluation. The integration of high-resolution imaging with biomolecular data significantly enhances diagnostic depth, paving the way for intelligent, patient-specific breast cancer management.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"544-552"},"PeriodicalIF":1.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruiyi Jing, Yuxi Nie, Yueling Wu, Chunhua Zhang, Qing Liu, Lei Bi, Weiping Chen
{"title":"Mapping the Intersection of Traditional Chinese Medicine and Ultrasound Therapies in Tumor Microenvironment Research (2014-2024): A Knowledge Atlas Study.","authors":"Ruiyi Jing, Yuxi Nie, Yueling Wu, Chunhua Zhang, Qing Liu, Lei Bi, Weiping Chen","doi":"10.1177/10849785251415289","DOIUrl":"10.1177/10849785251415289","url":null,"abstract":"<p><strong>Background: </strong>Traditional Chinese Medicine (TCM) and ultrasound-based therapy techniques have emerged as viable complementary approaches to cancer treatment, since both have modulatory effects on the tumor microenvironment (TME). TCM is distinguished by its multicomponent and multitarget processes, whereas ultrasound treatments provide noninvasive biophysical modification to improve medication transport, immunological activation, and vascular permeability. Despite growing recognition of the synergistic potential of these modalities, no comprehensive bibliometric examination of their confluence in TME research has yet been done.</p><p><strong>Methods: </strong>CiteSpace and VOSviewer were used to evaluate publications from the Web of Science Core Collection spanning from 2014 to 2024. A total of 771 relevant publications were used to create visual knowledge maps, highlight research hotspots, collaborative networks, and emerging trends, with a particular emphasis on studies that combined TCM and ultrasonography in cancer-related TME regulation.</p><p><strong>Results: </strong>Over the last decade, research at the interface of TCM and ultrasonic therapy has expanded rapidly. China has dominated this sector in terms of publication volume and worldwide influence, with strong partnerships with the United States and the United Kingdom. The core institutions include the Shanghai University of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Zhejiang University, Shanghai Jiao Tong University, and the Chinese Academy of Sciences. The research field has shifted from basic studies on \"cell proliferation\" and \"apoptosis\" to more sophisticated inquiries into \"immune microenvironment regulation,\" \"ultrasound-assisted drug delivery,\" \"nanomedicine,\" and \"synergistic therapy.\"</p><p><strong>Conclusions: </strong>The combination of TCM and ultrasonic therapy in TME research represents a new multidisciplinary frontier that combines molecular biology, materials science, and clinical oncology. This bibliometric and knowledge atlas study emphasizes the expanding body of data supporting ultrasound-enhanced TCM therapies as a promising paradigm in cancer therapy. To fully realize their combined promise in precision oncology, future initiatives should focus on mechanistic validation, standardized clinical evaluation, and worldwide collaboration.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"515-527"},"PeriodicalIF":1.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ultrasound-Enhanced CRISPR-Curcumin Nanoparticles for Gene-Modulating Therapy in Metastatic Pulmonary Lesions.","authors":"Xinwen Xu, Xue Yu, Kai Zhang, Ying Zhang","doi":"10.1177/10849785261433852","DOIUrl":"10.1177/10849785261433852","url":null,"abstract":"<p><strong>Background: </strong>Curcumin exhibits strong gene-regulatory, epigenetic-modulating, and oncogene-suppressive properties, but its poor aqueous solubility and low intracellular bioavailability limit therapeutic application. Gene-targeted nanodelivery platforms combined with ultrasound-mediated permeabilization provide a promising approach to enhance the precision and potency of curcumin-based gene therapy. This study evaluates CRISPR-supported, curcumin-loaded polymeric nanoparticles (CRISPR-CuNPs) designed to silence the KRAS-G12D oncogene while enhancing tumor-suppressor gene expression (TP53, PTEN) in metastatic pulmonary cancer cells, using experimentally optimized ultrasound conditions validated for delivery efficiency and cellular safety.</p><p><strong>Methods: </strong>Curcumin-loaded polymeric nanoparticles were co-formulated with plasmid DNA encoding CRISPR/Cas9 elements targeting KRAS-G12D and delivered to cancer cells with or without experimentally optimized low-intensity pulsed ultrasound (1 MHz, 0.5 W/cm<sup>2</sup>). Nanoparticle characterization included size, zeta potential, polydispersity index, and encapsulation effectiveness. Nanoparticle stability, morphology, and plasmid retention were evaluated under physiological temperature and serum conditions before and after ultrasound exposure. Intracellular uptake, endosomal escape, and nuclear localization were quantified using luminescence microscopy and flow cytometry. Gene silencing and gene improvement were analyzed using qPCR, Western blotting, and chromatin immunoprecipitation assays for epigenetic profiling. The MTT, Annexin V, and three-dimensional tumor models were used to assess cytotoxicity, apoptosis, and spheroid loss, respectively.</p><p><strong>Results: </strong>After ultrasound exposure, CRISPR-CuNPs showed a 2.7-fold increase in nuclear-associated nanoparticle fluorescence, suggesting improved endosomal escape and nuclear entry for effective gene delivery and modulation. A low polydispersity index (0.18 ± 0.02) determined by dynamic light scattering minimized variability in uptake across replicate organs. KRAS mRNA and protein levels were reduced by 72 ± 4%, with greater suppression observed in CRISPR-CuNP-treated cells compared with curcumin-only controls, confirming CRISPR-mediated gene disruption. Curcumin-mediated chromatin remodeling was evidenced by enrichment of H3K27ac at TP53 and PTEN promoters, resulting in upregulation of TP53 (3.5-fold) and PTEN (2.8-fold). Ultrasound-enhanced CRISPR-CuNPs further increased KRAS protein repression to 90 and elevated PTEN expression 46-fold. Apoptosis induction reached 87 ± 3, synergistic interaction between KRAS silencing and epigenetic activation of tumor-suppressor pathways, while metastatic lung cancer spheroids showed an 80% reduction in viable tumor volume. Minimal γ-H2AX induction indicated low acute DNA damage, supporting short-term genomic safety.</p><p><strong>Conclusions: </strong>Ultrasound-stimulate","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"505-514"},"PeriodicalIF":1.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147516891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ultrasound-Responsive Folate-Chlorogenic Acid Nanocarrier Targeting Mixed Lineage Kinase 1 for Enhanced Wilms Tumor Therapy.","authors":"Yanjiao Tang, Yunting Meng, Xiaomin Huang, Xinyue Zheng, Qian Wu, Weihao Xiao, Yuxi Huang, Xingchen Ming, Jiangling Yao","doi":"10.1177/10849785261424783","DOIUrl":"10.1177/10849785261424783","url":null,"abstract":"<p><strong>Background: </strong>Wilms tumor (nephroblastoma) is the most frequent malignant tumor of the urinary system in children; however, current treatment choices are restricted due to inadequate drug targeting, systemic toxicity, and multidrug resistance. Chlorogenic acid (CGA), a natural polyphenolic molecule, has promise as an anti-Wilms tumor action but has limited water solubility and bioavailability. To address these constraints, the authors created an ultrasound-responsive folate-CGA nanocarrier (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-folic acid-CGA [DSPE-PEG-FA/CGA]) that enables targeted and regulated drug administration.</p><p><strong>Methods and results: </strong>The nanocarrier was created utilizing DSPE as the structural backbone, with PEG modification for increased stability and FA conjugation for tumor-specific targeting. Following low-intensity ultrasonic treatment, the nanocarrier increased permeability and induced CGA release via acoustic cavitation effects, greatly enhancing local drug accumulation inside tumor tissues.Ultrasound Augmentation:Comprehensive characterization demonstrated good encapsulation efficiency, consistent particle size, and acceptable ultrasonic responsiveness. <i>In vitro</i> experiments indicated increased cellular absorption via folate receptor-mediated endocytosis and ultrasound stimulation, leading to more cytotoxicity against Wilms tumor cells than nonultrasound-treated controls. <i>In vivo</i>, the DSPE-PEG-FA/CGA system demonstrated selective tumor accumulation, dose-dependent tumor growth suppression, and good biosafety in nude mice, with no changes in body weight or organ damage. Mechanistic research revealed mixed-lineage kinase 1 (MLK1) as a direct molecular target of CGA, since it binds to MLK1's active pocket (specifically residues L303, I228, and A249) and modifies the MAPK and PI3K-Akt signaling pathways to induce apoptosis and decrease proliferation.</p><p><strong>Conclusions: </strong>Overall, this work shows that ultrasound-responsive folate-CGA nanotherapy is an effective, safe, and focused method for treating Wilms tumors by combining molecular suppression of MLK1 with ultrasound-enhanced delivery accuracy.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"490-504"},"PeriodicalIF":1.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147482466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pengfei Xu, Xianfu Lin, Yunhai Zhu, Jinyuan Chen, Bo Yang
{"title":"Prognostic Factor Analysis and Nomogram Development in Castration-Resistant Prostate Cancer with Visceral Metastases for Future Radionuclide Therapy Selection.","authors":"Pengfei Xu, Xianfu Lin, Yunhai Zhu, Jinyuan Chen, Bo Yang","doi":"10.1177/10849785261460356","DOIUrl":"https://doi.org/10.1177/10849785261460356","url":null,"abstract":"<p><strong>Objective: </strong>To identify independent prognostic factors in castration-resistant prostate cancer (CRPC) patients with visceral metastases, construct and internally validate a prognostic nomogram for individualized risk stratification, and generate a hypothesis-driven framework that may inform future candidate selection for radionuclide therapies-including lutetium-177 PSMA-617 (<sup>177</sup>Lu-PSMA-617) and radium-223 dichloride (<sup>223</sup>Ra)-pending prospective targeted radionuclide therapy (TRT)-specific validation.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted on 98 CRPC patients with imaging-confirmed visceral metastases treated at the institution from January 2017 to December 2023. Baseline demographics, tumor parameters, laboratory biomarkers, and treatment data were systematically collected. The primary endpoint was overall survival (OS); the secondary endpoint was progression-free survival (PFS). Kaplan-Meier analysis, univariate and multivariate Cox proportional hazards regression models, and a six-factor prognostic nomogram were used. Model performance was assessed by Concordance Index (C-index), bootstrap-corrected calibration curves (1000 iterations), and time-dependent receiver operating characteristic analysis.</p><p><strong>Results: </strong>Among 98 patients (median age 68 years), median follow-up was 19.2 months, with 72 deaths (73.5%). Median OS was 13.2 months (95% confidence interval [CI]: 11.5-15.0 months); median PFS was 7.5 months (95% CI: 6.6-8.5 months). Six independent adverse prognostic factors for OS were identified: Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (hazard ratio [HR] = 1.89, <i>p</i> < 0.001), multiorgan visceral metastases (HR = 1.52, <i>p</i> = 0.008), alkaline phosphatase<b> </b>≥240 U/L (HR = 1.58, <i>p</i> = 0.004), hemoglobin <110 g/L (HR = 1.45, <i>p</i> = 0.024), albumin <35 g/L (HR = 1.62, <i>p</i> = 0.004), and prostate-specific antigen decline <50% (HR = 1.78, <i>p</i> < 0.001). The nomogram achieved a C-index of 0.712 (OS) and 0.698 (PFS); time-dependent area under the curve (AUC) ranged from 0.672 to 0.748 across 6-24 months.</p><p><strong>Conclusions: </strong>CRPC patients with visceral metastases carry a dismal prognosis. The six-factor nomogram provides a quantitative prognostic framework that may support evidence-based risk stratification in this high-risk subpopulation. Important to note that no patient in this cohort received radionuclide therapy; the model is derived from a non-TRT cohort and should be regarded as hypothesis generating. Its utility as a TRT selection instrument warrants prospective validation in cohorts receiving <sup>177</sup>Lu-PSMA-617 or <sup>223</sup>Ra. Integration with molecular biomarkers-prostate-specific membrane antigen (PSMA) expression quantification, AR-V7 status, and DNA damage repair profiling-remains essential for future validation.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"10849785261460356"},"PeriodicalIF":1.7,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of a <sup>177</sup>Lu-Labeled Glypican-3-Targeted Antibody Radiopharmaceutical for Adjuvant Radionuclide Therapy Following Hepatocellular Carcinoma Resection.","authors":"Ke Fang","doi":"10.1177/10849785261458520","DOIUrl":"https://doi.org/10.1177/10849785261458520","url":null,"abstract":"<p><p><i>Background:</i> Hepatocellular carcinoma (HCC) remains the major cause of cancer-related mortality worldwide due to high postoperative recurrence rates and limited treatment options for minimal residual disease (MRD).<i>Methods:</i> In this study, glypican-3 (GPC3)-targeted radiopharmaceutical, <sup>177</sup>Lu-DOTA-GPC3, was developed and evaluated as a potential adjuvant targeted radionuclide therapy for HCC. The anti-GPC3 monoclonal antibody was conjugated with DOTA and radiolabeled with <sup>177</sup>Lu under systematically optimized conditions. Optimization of the chelator-to-antibody ratio, pH, temperature, and incubation time was performed to maximize the radiochemical yield while preserving antibody immunoreactivity and structural integrity. The radioconjugate was purified and characterized using instant thin-layer chromatography and size-exclusion high-performance liquid chromatography. <i>In vitro</i> stability was assessed in phosphate-buffered saline and human serum, while cellular binding and internalization studies were conducted using GPC3-expressing HepG2 cells. <i>In vivo</i> biodistribution, pharmacokinetics, and therapeutic efficacy were evaluated in the tumor-bearing mice.<i>Results:</i> The developed radioconjugate demonstrated high radiolabeling efficiency (96.8% ± 1.2%) and radiochemical purity (>98%) with excellent stability (>95% up to 72 h). Batch-to-batch reproducibility showed minimal variability across independent preparations. Strong receptor-specific cellular binding (∼82%) and significant internalization were observed, confirming preservation of the biological activity following radiolabeling. Biodistribution studies demonstrated high tumor uptake (18.6% ± 2.1%ID/g at 48 h) with favorable tumor-to-background ratios. Therapeutic evaluation revealed up to 66.4% tumor growth inhibition and significantly prolonged survival without observable systemic toxicity.<i>Conclusions:</i> Findings support the potential of the <sup>177</sup>Lu-DOTA-GPC3 as a promising theranostic radionuclide platform for targeting GPC3-positive HCC and addressing postoperative MRD-associated recurrence.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"10849785261458520"},"PeriodicalIF":1.7,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qi Fan, Zhengwei Fu, Ming Xu, Zan Luo, Dehai Xiong
{"title":"Synergistic Mechanisms and Clinical Progress of Radionuclide Therapy Combined with Immune Checkpoint Inhibitors in Colorectal Cancer.","authors":"Qi Fan, Zhengwei Fu, Ming Xu, Zan Luo, Dehai Xiong","doi":"10.1177/10849785261466877","DOIUrl":"https://doi.org/10.1177/10849785261466877","url":null,"abstract":"<p><p><i>Background:</i> Radionuclide therapy (RNT) and immune checkpoint inhibitors (ICIs) show mechanistic synergy in colorectal cancer (CRC), but clinical evidence remains limited.<i>Objective:</i> To summarize biological rationale, translational mechanisms, and current clinical evidence supporting RNT-ICI combinations in CRC.<i>Methods:</i> Narrative translational review integrating preclinical studies, radionuclide therapy literature, and CRC radiotherapy-ICI clinical trials.<i>Results:</i> ICIs are effective mainly in MSI-H/dMMR CRC, whereas MSS/pMMR tumors remain resistant. RNT-particularly Y-90 radioembolization-may induce immunogenic cell death, cGAS-STING activation, type I interferon signaling, and stromal remodeling. A pilot clinical study of Y-90 plus dual ICIs demonstrated feasibility and safety but limited efficacy. Evidence from EBRT-ICI CRC studies supports radiation-induced immune priming but is not directly transferable to RNT.<i>Conclusion:</i> RNT-ICI combinations are biologically plausible but not yet clinically validated. Future progress requires biomarker-driven, dosimetry-informed, and liver-dominant trial designs.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"10849785261466877"},"PeriodicalIF":1.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}