Cancer Biotherapy and Radiopharmaceuticals最新文献

{"title":"Characterization of Adverse Drug Effects to Three Radiopharmaceuticals: A Descriptive Analysis from WHO-VigiAccess.","authors":"Yiheng Jin, Kunlun Gui, Kaixin Chen, Xiaowu Wang, Xinlong Wan, Shugen Qu","doi":"10.1177/10849785261446231","DOIUrl":"https://doi.org/10.1177/10849785261446231","url":null,"abstract":"<p><strong>Background: </strong>Radiopharmaceuticals are being used more frequently to treat neuroendocrine tumors and advanced prostate cancer; however, their clinical application is associated with adverse drug reactions (ADRs) that may affect patient safety. Real-world data from spontaneous reporting systems such as the World Health Organization's (WHO's)-VigiAccess can aid in assessing safety after the drugs have been marketed.</p><p><strong>Materials and methods: </strong>A retrospective descriptive analysis was conducted using ADR reports from the WHO-VigiAccess database up to November 2024. Reports related to lutetium (¹⁷⁷Lu) dotatate (Lutathera^®), lutetium (¹⁷⁷Lu) vipivotide tetraxetan (Pluvicto^®), and radium (²²³Ra) dichloride (Xofigo^®) were extracted and analyzed with respect to patient demographics, geographic distribution, and ADRs classified by MedDRA System Organ Class and Preferred Terms. Descriptive statistics were used to compare safety profiles.</p><p><strong>Results: </strong>A total of 17,743 ADR reports were analyzed. Lutathera was predominantly associated with gastrointestinal disorders and skin or subcutaneous tissue reactions. In contrast, Pluvicto demonstrated a higher frequency of general systemic disorders and a disproportionately higher number of fatal outcomes, a finding consistent with its indication for the treatment of advanced prostate cancer. Xofigo was primarily linked to hematological and musculoskeletal toxicities. In addition to 169 ADRs that were common to all three agents, distinct drug-specific reaction patterns were also observed.</p><p><strong>Conclusions: </strong>WHO-VigiAccess data reveal clearly differentiated ADR profiles among Lutathera, Pluvicto, and Xofigo. These results highlight the necessity for individualized risk assessment, careful monitoring, and further prospective investigations to optimize the safe clinical application of radiopharmaceuticals.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"10849785261446231"},"PeriodicalIF":2.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846456","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":"On the Importance of Extracting the Needle from the Haystack.","authors":"Martin W Brechbiel, Alan G Harris, Craig H Sherman","doi":"10.1177/10849785261448799","DOIUrl":"https://doi.org/10.1177/10849785261448799","url":null,"abstract":"","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"10849785261448799"},"PeriodicalIF":2.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846165","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":"Cavitation-Free Acoustic Sensitization Enhances PLK4-Targeted Therapy Using the Phillyrin Derivative DE02 in Osteosarcoma.","authors":"Jin Yang, Haoyu Wang, Zongyun He, Wei Wang, Jun Qian","doi":"10.1177/10849785261446291","DOIUrl":"https://doi.org/10.1177/10849785261446291","url":null,"abstract":"<p><strong>Objective: </strong>To ascertain whether cavitation-free acoustic sensitization enhances intracellular delivery and amplifies polo-like kinase 4 (<i>PLK4</i>)-targeted signaling to boost the phillyrin derivative DE02's antitumor efficacy against osteosarcoma, providing a secure and effective ultrasound-enabled method for targeted cancer biotherapy.</p><p><strong>Methods: </strong>Using ultracentrifugation, exosomes generated from human umbilical vein endothelial cells were separated, purified, and identified using common morphological and molecular markers. Low-energy sonication under cavitation-free acoustic circumstances was used to insert DE02 into exosomes, creating an exosomal delivery (ExoDE02) system intended to improve cellular absorption without causing membrane damage. MG-63 and Saos-2 human osteosarcoma cell lines were used as <i>in vitro</i> models. The cell counting kit-8 test was used to measure cell proliferation, proliferating cell nuclear antigen (<i>PCNA</i>) immunofluorescence was used to measure proliferative activity, and Transwell assays were used to measure migration and invasion. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative PCR, and Western blotting were used to assess the expression of <i>PLK4</i> and downstream <i>tumor protein 53 (p53)-cyclin-dependent kinase inhibitor 1A (p21)</i> signaling components. To verify pathway specificity, <i>PLK4</i> overexpression studies were carried out. A nude mouse xenograft model was used to evaluate <i>in vivo</i> antitumor effectiveness and biosafety.</p><p><strong>Results: </strong>In a concentration-dependent manner, DE02 showed almost 10 times more antiproliferative action against osteosarcoma cells than the parent chemical phillyrin. The inhibitory effects of DE02 on osteosarcoma cell proliferation, migration, and invasion were greatly enhanced by cavitation-free acoustic sensitization-mediated ExoDE02. This was accompanied by a significant downregulation of <i>PCNA</i> and <i>PLK4</i> expression and activation of the <i>p53-p21</i> tumor suppressor pathway. The anticancer effects of DE02 and ExoDE02 were successfully inhibited by overexpression of <i>PLK4</i>, indicating <i>PLK4</i>-dependent therapeutic efficacy. ExoDE02 significantly inhibited the growth of xenograft tumors <i>in vivo</i>, decreased tumor weight and volume, and showed no discernible systemic toxicity.</p><p><strong>Conclusions: </strong>By increasing the therapeutic efficacy of the phillyrin derivative DE02 via a safe, nondestructive exosome-based delivery method, cavitation-free acoustic sensitization improves <i>PLK4</i>-targeted osteosarcoma therapy. For targeted osteosarcoma biotherapy, this ultrasound-enabled method provides a mechanistically defined and physiologically applicable platform.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"10849785261446291"},"PeriodicalIF":2.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846525","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":"Expanding the Therapeutic Window in Oncology: Modern Strategies and Future Directions.","authors":"Shital Dange, Mohammed Musharraf Ali, Mamatha Gavisiddaiah, Jaffer Sadik Mohamed, Nasreen Sulthana, Roja Pathakota, Chandrika Balija","doi":"10.1177/10849785261445412","DOIUrl":"https://doi.org/10.1177/10849785261445412","url":null,"abstract":"<p><p><i>Background:</i>The enhancement of the therapeutic window (TW) in oncology remains a significant challenge, as the majority of anticancer treatments face difficulties in achieving optimal tumor control while minimizing adverse effects. Traditional chemotherapeutic agents, while demonstrating efficacy, are constrained by their limited TWs and the occurrence of systemic adverse effects.<i>Objective:</i> Recent advancements in precision medicine have revolutionized this paradigm by facilitating targeted tumor intervention via molecularly guided therapies, immuno-oncology strategies, and biomarker-driven patient classification. Novel approaches, including nanomedicine, antibody-drug conjugates, and prodrug formulations, improve therapeutic selectivity through the optimization of drug delivery, biodistribution, and release kinetics.<i>Methodology:</i> The concurrent advancements in radiotherapy, adaptive dosing methodologies, and toxicity assessment instruments have expanded the potential to enhance treatment intensity while preserving the integrity of normal tissues. In the future, the convergence of artificial intelligence (AI), multiomics profiling, and systems biology is anticipated to enhance therapeutic decision-making and expedite the creation of more personalized and adaptive interventions.<i>Results:</i>The efficacy of cancer treatments is substantially limited by notable shortcomings in research, despite progress in precision oncology. Tumor heterogeneity, the emergence of resistance mechanisms, and the absence of reliable biomarkers for anticipating treatment outcomes present significant impediments. The utilization of multiomics data and AI in clinical decision-making remains in its early stages, constrained by limitations in data validation and standardization. Furthermore, the translation of transdisciplinary concepts into accessible treatments is crucial, especially in environments with limited resources. Consequently, addressing these multifaceted issues is essential for improving the efficacy and safety of cancer treatments.<i>Conclusion:</i>This review integrates contemporary strategies and examines prospective pathways for expanding the TW, highlighting the intersection of technology, biology, and clinical innovation in the progression of cancer treatment.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"10849785261445412"},"PeriodicalIF":2.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846189","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":"Precision Oncology with ¹⁷⁷Lu-PSMA-617 Radionuclide Therapy in Elderly Patients with Metastatic Castration-Resistant Prostate Cancer.","authors":"Fayou Zhou, Yongqing Zheng, Liang Huang, Xiaolei Tang, Liwei Yang, Sheng Shao","doi":"10.1177/10849785261447847","DOIUrl":"https://doi.org/10.1177/10849785261447847","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate the treatment response status in elderly patients with metastatic castration-resistant prostate cancer (mCRPC) receiving &lt;sup&gt;177&lt;/sup&gt;Lu-PSMA-617 radioligand therapy within a precision oncology framework, analyze the incidence, depth, and influencing factors of PSA and radiological response, and provide scientific evidence for developing individualized treatment selection and optimization strategies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A cross-sectional survey study was conducted, including 182 elderly patients (age ≥65 years, having completed ≥2 cycles of &lt;sup&gt;177&lt;/sup&gt;Lu-PSMA-617 therapy) with prostate-specific membrane antigen (PSMA)-positive mCRPC confirmed by &lt;sup&gt;68&lt;/sup&gt;Ga-PSMA-11 Positron emission tomography/Computed tomography (PET/CT). Standardized assessment tools, including the Functional Assessment of Cancer Therapy-Prostate (FACT-P), Brief Pain Inventory-Short Form, and Hospital Anxiety and Depression Scale, were used to evaluate treatment response, quality of life, and mental health. The Common Terminology Criteria for Adverse Events was applied to grade treatment-related toxicities. Univariate analysis was performed to screen influencing factors, and multivariate logistic regression analysis was conducted to identify independent predictors of treatment response.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The overall PSA50 response rate (≥50% PSA decline) was 63.7% (116/182). Moderate response (50%-89% PSA decline) accounted for 39.6%, and deep response (≥90% PSA decline) accounted for 24.2%. Radiological partial or complete response was achieved in 42.3% of patients. Patients in the response group showed significantly higher FACT-P total scores (115.6 ± 18.4 versus 84.2 ± 17.8, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and lower anxiety, depression, and pain scores compared with the nonresponse group. Multivariate analysis identified baseline hemoglobin &lt; 100 g/L (OR = 2.19, 95% CI: 1.05-4.57), prior docetaxel exposure (OR = 2.18, 95% CI: 1.07-4.44), high tumor burden ≥ 10 lesions (OR = 2.35, 95% CI: 1.18-4.67), PSMA SUVmax &lt; 12 (OR = 2.39, 95% CI: 1.11-5.14), and baseline alkaline phosphatase (ALP) &gt; 200 U/L (OR = 2.13, 95% CI: 1.03-4.37) as independent predictors of treatment nonresponse. PSA50 response rate showed a significant increasing trend with the number of therapy cycles administered (χ&lt;sup&gt;2&lt;/sup&gt;trend = 5.214, &lt;i&gt;p&lt;/i&gt; = 0.022).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Elderly mCRPC patients undergoing &lt;sup&gt;177&lt;/sup&gt;Lu-PSMA-617 radioligand therapy achieve meaningful PSA50 response rates, with baseline hemoglobin, prior docetaxel exposure, tumor burden, PSMA expression level, and ALP being independent predictors of response. Treatment response is closely associated with improved quality of life and mental health outcomes, with response rates improving with additional therapy cycles. These findings provide evidence-based guidance for precision patient selection, treatment monitoring, and individualized optimization st","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"10849785261447847"},"PeriodicalIF":2.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846199","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":"Radiopharmaceutical Oncology Care Supported by Ultrasound-Guided Superior Vena Cava-Right Atrial Junction Port Tip Positioning in Adult Cancer Patients.","authors":"Quan Ling, Yinqi Yang, Junlin Wen, Jin Liu, Yong Chen","doi":"10.1177/10849785261442223","DOIUrl":"https://doi.org/10.1177/10849785261442223","url":null,"abstract":"<p><p><i>Background:</i> In this single-center retrospective study, the authors evaluated whether real-time ultrasound-guided positioning of an implantable venous access port catheter tip at the superior vena cava-right atrial junction (SVC-RAJ) reduces the risk of catheter-related thrombosis (CRT) in adult patients with cancer and developed a multivariable risk prediction model to support individualized prevention.<i>Methods:</i> Clinical data from 600 consecutive patients who underwent port implantation at Zhongshan People's Hospital were analyzed. Patients were grouped according to final catheter tip position (SVC-RAJ versus non-SVC-RAJ), and CRT incidence was compared between groups.<i>Results:</i> The overall incidence of CRT was 30.33% (182/600) and was significantly lower in the SVC-RAJ group than in the non-SVC-RAJ group (22.42% vs. 38.73%, <i>p</i> < 0.001). In multivariable analysis, catheter tip positioning at the SVC-RAJ remained an independent protective factor (odds ratio = 0.517, 95% confidence interval [CI]: 0.353-0.756). Age, body mass index (BMI), tumor stage, neutrophil-to-lymphocyte ratio, D-dimer level, catheterization duration, and prophylactic anticoagulation status were also independently associated with CRT. A nomogram integrating these variables demonstrated good discrimination (area under the curve = 0.866, 95% CI: 0.837-0.895), with a sensitivity of 70.33% and a specificity of 85.89%. Performance across specific age or BMI strata was not separately evaluated in this study, and further stratified validation in larger datasets is needed to assess model consistency across demographic subgroups.<i>Conclusions:</i> These findings support ultrasound-guided SVC-RAJ positioning as a clinically relevant strategy for reducing CRT risk and maintaining reliable venous access in contemporary oncology care pathways.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"10849785261442223"},"PeriodicalIF":2.1,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822937","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":"Radiopharmaceutical-Guided Personalized Adjuvant Radiotherapy Planning after Esophageal Cancer Resection.","authors":"Zhida Fu, Yinghui Fang, Dapeng Wang, Jianxin Zuo, Shuaishuai Xiao, Jingyang Si","doi":"10.1177/10849785261443946","DOIUrl":"https://doi.org/10.1177/10849785261443946","url":null,"abstract":"<p><strong>Background: </strong>Esophageal cancer often has a significant locoregional recurrence risk after curative resection. Conventional postoperative radiation is largely based on anatomical imaging, which may not adequately detect microscopic residual disease or biological tumor heterogeneity.</p><p><strong>Purpose/hypothesis: </strong>The incorporation of radiopharmaceutical-guided molecular imaging enables biologically adaptive dosage adjustment.</p><p><strong>Population/subjects: </strong>The study assesses the feasibility and therapeutic efficiency of radionuclide-informed individualized adjuvant radiation planning following esophageal cancer resection.</p><p><strong>Assessment: </strong>Positron Emission Tomography (PET)/Computed Tomography (CT) imaging with tumor-specific tracers enabled the identification of biological targets.</p><p><strong>Statistical tests: </strong>Voxel-based dose painting was used, and plans were compared using the conformity index (CI), homogeneity index, V95% coverage, tumor control probability (TCP), and normal tissue complication probability (NTCP). Radiopharmaceutical imaging revealed additional high-risk areas in 34.7% of patients. Personalized planning increased the CI (1.21 to 0.97), V95% (91.2% to 97.8%), and TCP (68.4% to 82.9%). Mean lung and heart doses decreased by 14.3% and 11.7%, respectively, decreasing the predicted NTCP for pneumonitis from 16.5% to 9.2% (<i>p</i> < 0.001).</p><p><strong>Results: </strong>Radionuclide-guided personalized adjuvant radiation improves biological target coverage, increases TCP, and minimizes normal tissue toxicity, hence confirming its role in precision postoperative management of esophageal cancer.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"10849785261443946"},"PeriodicalIF":2.1,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822914","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":"CavitoMod-UTMDNet: A Mechanistic Cavitation-Diffusion Framework for Ultrasound-Targeted Microbubble Destruction-Enhanced Liposomal Doxorubicin Delivery in Pancreatic Cancer.","authors":"Yazeed Alashban, Ghada Moh Samir Elhessewi, Mohammed Maray, Ali M Al-Sharafi, Hanadi Alkhudhayr, Rana Alabdan, Nujud Aloshban, Shouki A Ebad","doi":"10.1177/10849785261431195","DOIUrl":"https://doi.org/10.1177/10849785261431195","url":null,"abstract":"<p><p><i>Background:</i> Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest treatment responses since it contains desmoplastic stroma, lacks good vascularity, and has high interstitial fluid pressures, which are the most damaging factors depriving chemotherapy. Liposomal doxorubicin is much better in terms of systemic pharmacokinetics but is not efficient in PDAC due to the significant barrier of nanoparticles-stromal and vascular barriers.<i>Purpose/Hypothesis:</i> In a bid to eliminate these shortcomings, this paper presents CavitoMod-UTMDNet, which is an integrated mechanistic and experimental platform capable of utilizing ultrasound-targeted masterpiece unaffiliating (UTMD) as a means of temporarily improving vascular and stromal permeability and better intratumoral delivery of liposomal doxorubicin.<i>Population/Subjects:</i> The model combines Rayleigh-Plesset cavitation modeling and Fickian diffusion analysis with a two-compartment pharmacokinetic model and systematic in vitro and in vivo validation.<i>Assessment:</i> Passive cavitation detection was used to establish stable cavitation exposure windows within FDA-acceptable mechanical index limits.<i>Statistical Tests:</i> UTMD increased intracellular drug uptake 3.2-3.8fold and reduced IC 0 in PANC-1 and BxPC-3 pancreatic cancer cell lines by around 50% in the presence of a stable cavitation (MI 1.2). UTMD progressively improved the level of intratumor drug delivery in the orthotopic immunodeficient mouse models (NU/NU strain) (2.4-fold) and led to a 54% decrease in tumor volume 21 days later without any trace of hepatic, renal, and cardiac toxicity.<i>Results:</i> There were strong links between cavitation energy density and drug uptake and diffusion depth and therapeutic response as evidence that there is a mechanistic character to UTMD-enhanced actions. It will support the drug development in a better way. CavitoMod-UTMDNet is a combined strategy to maximize ultrasound-enhanced nanocarrier (nanoparticles) delivery using a physics-based reproducible plan to optimize ultrasound-enhanced nanocarrier delivery in PDAC that will see improvement in future translation to image-guided therapeutic strategies.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"10849785261431195"},"PeriodicalIF":2.1,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678465","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":"Clinical Evaluation of Ultrasound-Enhanced Radiotracer Uptake for Radioligand Therapy in Metastatic Prostate Cancer.","authors":"Yangbing Liang, Qingguo Wu, Yiwen Liang, Hanchu Ji","doi":"10.1177/10849785261431192","DOIUrl":"https://doi.org/10.1177/10849785261431192","url":null,"abstract":"<p><strong>Background: </strong>Low-intensity pulsed ultrasound (LIPUS) may noninvasively enhance intratumoral delivery of radiopharmaceuticals, but clinical data are scarce. The authors prospectively evaluated whether adding LIPUS to prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) improves uptake and outcomes in metastatic prostate cancer while maintaining safety.</p><p><strong>Methods: </strong>A total of 42 men with PSMA PET-positive metastatic prostate cancer received up to six cycles of ¹⁷⁷Lu-PSMA-617. Before each infusion, LIPUS (1 MHz, 0.5-2.0 W/cm², 10 min) was applied to one dominant metastasis. Baseline and postcycle-1 PSMA PET/CT measured percent change in SUV_max (ΔSUV_max) for the sonicated lesion versus a matched nonsonicated reference lesion. Patients were classified as high (ΔSUV_max ≥20%) or low enhancement. Prostate-specific antigen (PSA) response, progression-free survival (PFS), and toxicity were recorded.</p><p><strong>Results: </strong>LIPUS was feasible in all patients without treatment interruptions. Sonicated lesions showed higher uptake (median ΔSUV_max + 32%) than reference lesions (+3%; <i>p</i> < 0.001). High-enhancement patients had more PSA_50 responses (71% vs. 33%) and longer PFS (11.5 vs. 5.3 months; hazard ratio 0.35). Adverse events were mainly Grades 1-2 local discomfort and typical ¹⁷⁷Lu-PSMA toxicities; no Grade ≥3 LIPUS-related events occurred.</p><p><strong>Conclusions: </strong>US-enhanced RLT appears safe and can increase intratumoral radiotracer uptake, translating into improved biochemical control and PFS in metastatic prostate cancer.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"10849785261431192"},"PeriodicalIF":2.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655367","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-Assisted Radiopharmaceutical Investigation of GNL1-Mediated AKT-P53-P21 Axis Activation in Cervical Cancer Progression.","authors":"Yingying Jiang, Jing Ren, Junzhen Tao","doi":"10.1177/10849785261438424","DOIUrl":"https://doi.org/10.1177/10849785261438424","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer is a leading cause of cancer death in women worldwide, and the outcomes for advanced or recurrent disease remain poor. Ultrasound-assisted delivery could increase intratumoral uptake of radiopharmaceuticals, but prospective clinical evidence and risk data are limited.</p><p><strong>Methods: </strong>In a single-center pilot (<i>n</i> = 30), patients with advanced cervical cancer underwent paired PET/CT sessions 60 min after identical intravenous radiopharmaceutical injections: control (no ultrasound) and ultrasound-assisted delivery using 1 MHz focused ultrasound (FUS) for 10 min with microbubble cavitation monitoring. Uptake (SUV_max) and tumor-to-background ratio (TBR) were compared within patient; response used RECIST 1.1, and adverse events (AEs) used CTCAE v5.0. Paired biopsies quantified GNL1, phospho-AKT, p53, and p21 (H-score).</p><p><strong>Results: </strong>Ultrasound increased median index-lesion SUV_max by ∼28% (<i>p</i> < 0.001) with improved TBR. The objective response rate was 26.7% and the disease control rate was 76.7%. Median progression-free survival was 8.5 months (95% confidence interval, 6.2-11.8) and the 12-month overall survival was 75% (median not reached). Most AEs were Grades 1-2; 20% were Grade ≥3, with no treatment-related deaths. Post-ultrasound biopsies showed decreased GNL1 and phospho-AKT with increased p53 and p21, and Δp21 correlated with uptake gain.</p><p><strong>Conclusions: </strong>Nonablative FUS can safely enhance radiopharmaceutical uptake in cervical cancer and is associated with biomarker shifts consistent with p53/p21 pathway activation.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"10849785261438424"},"PeriodicalIF":2.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641014","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}