Objective: This study evaluated the clinical diagnostic efficacy of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) for recurrence and/or metastasis in patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) and analyzed its correlation with serum thyroglobulin (Tg), BRAF V600E mutation status, and postoperative clinical risk stratification. Method: A retrospective analysis was conducted on the 18 F-FDG PET/CT images and clinical data of 47 patients with RAIR-DTC. The diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated, and the receiver operating characteristic curve was used to determine the optimal cutoff value of Tg. The correlation between maximum standardized uptake value (SUV max ) and clinical pathological characteristics was analyzed. Results: For 18 F-FDG PET/CT in detecting RAIR-DTC recurrence/metastasis, the diagnostic sensitivity was 94.87%, specificity 64.71%, PPV 92.50%, and NPV 73.33%. Regarding Tg, the optimal cutoff value for predicting RAIR-DTC recurrence/metastasis was 29.6 ng/mL, with an area under the curve of 0.7677. Further subgroup analysis showed that the serum Tg level in the PET/CT-positive group (212.56 ± 102.90 ng/mL) was significantly higher than that in the PET/CT-negative group (86.53 ± 69.67 ng/mL; t = 2.119, p = 0.039). In terms of clinical stage, the PET/CT positivity rate was significantly higher in patients with advanced RAIR-DTC (clinical stage III/IV) than in those with early-stage disease (81.82% versus 57.14%; p = 0.033). Correlation analysis revealed a positive correlation between 18 F-FDG PET/CT- derived SUV max and clinical stage (Pearson correlation coefficient, r = 0.361, p = 0.042). Furthermore, the SUV max in the BRAF V600E -mutant group was significantly higher than that in the BRAF V600E wild-type group (7.84 ± 3.50 versus 3.85 ± 1.26; t = −4.219, p = 0.039). In addition, the detection rate of 18 F-FDG PET/CT for RAIR-DTC recurrence/metastasis was significantly superior to that of Iodine-131 ( 131 I) single-photon emission computed tomography/computed tomography (SPECT/CT) (88.89% versus 52.78%; Z = 2.652, p = 0.041). Conclusions: 18 F-FDG PET/CT exhibits high diagnostic efficacy for RAIR-DTC recurrence/metastasis, with its positivity and SUV max significantly correlated with serum Tg, clinical stage, and BRAF V600E mutation. Clinically, this supports three key strategies: (1) Prioritize 18 F-FDG PET/CT follow-up for patients with Tg > 29.6 ng/mL, BRAF V600E positivity or postoperative high risk; (2) consider treatment escalation for PET/CT-positive patients with SUV max > 7.0; and (3) combine 18 F-FDG PET/CT with 131 I SPECT/CT to guide personalized management of RAIR-DTC.
Background: Radionuclide therapy (RNT) and immune checkpoint inhibitors (ICIs) show mechanistic synergy in colorectal cancer (CRC), but clinical evidence remains limited.Objective: To summarize biological rationale, translational mechanisms, and current clinical evidence supporting RNT-ICI combinations in CRC.Methods: Narrative translational review integrating preclinical studies, radionuclide therapy literature, and CRC radiotherapy-ICI clinical trials.Results: 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.Conclusion: RNT-ICI combinations are biologically plausible but not yet clinically validated. Future progress requires biomarker-driven, dosimetry-informed, and liver-dominant trial designs.
BACKGROUND:Hepatocellular carcinoma (HCC) is a highly prevalent malignant tumor globally, with low survival rates in advanced stages. Therefore, early diagnosis and precision therapy are pivotal to improving patient prognosis. Glypican-3 (GPC3) acts as a specific molecular target for HCC, which is highly expressed in 70%-85% of HCC tissues but undetectable in normal liver tissues, hepatitis, liver cirrhosis, and other pathological conditions. This stringent expression regulation renders it an ideal tumor-specific target. MAIN CONTENT:Based on the biological properties of GPC3, various specific tumor imaging agents have been developed, covering multiple biomolecular types, including antibodies, peptides, and aptamers. This review systematically summarizes the research advances, application advantages, and existing challenges of three types of molecular imaging probes in the precise diagnosis and treatment of HCC. It focuses on the development strategies of these probes and evaluates their current limitations in light of key characterization parameters. CONCLUSION:This review aims to provide new research ideas for the precision diagnosis of HCC and promote the translation of clinical applications.
α-emitting radiopharmaceuticals are increasingly being evaluated as potential cancer therapeutics. In this study, the authors evaluated the distribution of thorium-227 ( 227 Th) and its first daughter nuclide, radium-223 ( 223 Ra), by analyzing tissue activity data from monkey studies from different antibody-based targeted thorium conjugates (hereafter called “conjugates”). This study clarified the extent of elimination by physical decay and redistribution from tissues for both radionuclides. In monkey biodistribution studies for four different conjugates, animals were sacrificed at multiple time points, and organ activities of 227 Th and 223 Ra were measured by direct γ counting. These values were compared to the maximally expected organ activities based on physical decay as the sole elimination path to evaluate the impact of redistribution from tissues. Whole-body activities in cancer patients, measured with high-purity germanium detectors during a first-in-human study of a CD22-targeting conjugate, were evaluated similarly to determine whether they aligned with the overall patterns seen in tissue data. The integrated analysis demonstrated that for all conjugates, the physical decay appeared to be the main elimination path for 227 Th without a strong redistribution from organs, whereas 223 Ra shows a fast and strong redistribution (≥90%) from most of the tissues except for bone (∼0%) and (large) intestine. The lack of redistribution from bone as well as the high radioactivity in the intestine is consistent with data obtained with 223 Ra chloride in monkeys and humans. These findings were independent of the assessed compound, target, dose, and administered activity. The observation in monkeys that physical decay is the main elimination path for 227 Th and that 223 Ra undergoes a fast additional elimination in a typical tissue was consistent with clinical whole-body radioactivity data. The overarching consistency of the findings regarding tissue redistribution of 227 Th and 223 Ra across different conjugates and the consistency with clinical observations of whole body radioactivity in patients emphasize the importance of considering the potential redistribution of long-lived daughter nuclides of radionuclides used in therapeutic applications in humans.
BACKGROUND:Pneumonia in immunocompromised patients with cancer is associated with high morbidity, diagnostic uncertainty, and poor short-term outcomes. Precision radiopharmaceutical approaches may improve lesion localization, biodistribution assessment, and patient-specific treatment planning in this vulnerable population group. METHODS:The authors conducted a prospective single-arm study of a DOTA-functionalized antimicrobial peptide radiolabeled with 177Lu in immunocompromised patients with cancer with severe pneumonia. The study evaluated the radiochemical performance, in vitro stability, clinical biodistribution, pulmonary lesion localization, quantitative uptake kinetics, lesion dosimetry, short-term clinical response, and safety. The full cohort included 50 patients, with imaging- and dosimetry-evaluable subgroups of 5 and 15 patients, respectively. RESULTS:The radiopharmaceutical demonstrated high radiochemical purity (98.5%) and favorable labeling efficiency, with optimal radiolabeling achieved at 60°C. Whole-body planar imaging and thoracic SPECT/CT revealed persistent pulmonary lesion uptake with improved delayed lesion conspicuity. In the imaging subgroup, the lesion-to-blood pool and lesion-to-normal lung ratios increased over time, indicating progressive lesion contrast. Dosimetric analysis showed the highest absorbed dose in pulmonary lesions (∼4.5 Gy/GBq), exceeding the doses to the kidneys, liver, normal lung, and blood. Eleven of the 15 dosimetry-evaluable patients exceeded the predefined lesion-to-kidney dose ratio threshold of >2.0. Clinically, 35 of the 50 patients (70%) improved, 10 (20%) remained stable, and 5 (10%) worsened. No grade 4 adverse events were observed, and treatment-related toxicities were predominantly grades 1-2. CONCLUSIONS:177Lu-labeled antimicrobial peptide imaging demonstrated favorable radiochemical characteristics, persistent pulmonary lesion targeting, clinically relevant dosimetric selectivity, and an acceptable short-term safety profile in immunocompromised patients with cancer with severe pneumonia. These findings support the translational potential of this peptide-based radiopharmaceutical as a theranostic platform for imaging-guided dosimetry-informed precision management.
BACKGROUND:Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF), was lyophilized and radiolabeled with 99mTc for tumor-targeted imaging. In this study, a freeze-dried kit was developed, the formulation was optimized, and the radiolabeled bevacizumab was evaluated in vitro and in vivo for preclinical evaluation. METHODS:The preparation process was optimized by investigating pH, temperature, time, and stabilizers. The radiochemical purity (RCP) and immunoreactivity of the lyophilized antibody were determined and confirmed by specific binding to VEGF immobilized on Ni-NTA agarose. Preclinical evaluations included binding assays on three human cancer cell lines (A-549, MCF-7, and HT-29), in which binding affinity (Kd) and maximum binding capacity (Bmax) were calculated. Biodistribution studies were performed in normal mice. RESULTS:The optimized kit contained 2.0 mg bevacizumab per vial in phosphate buffer at pH 7.5, ensuring reproducible reconstitution and high labeling efficiency. Quality control demonstrated RCP >97% and in vitro stability of 99mTc-bevacizumab for at least 6 h post-labeling, with the freeze-dried form stable for 12 months. The 99mTc-bevacizumab retained >90% immunoreactivity. Binding assays revealed approximately 80% specific binding, with a Kd of 2.8-9.9 nM and a Bmax of 1.6-2.0 amol/cell, corresponding to about one million molecules per cell. Biodistribution revealed high initial blood retention, which was moderate in the liver, with a blood clearance half-life of 76.97 min, primarily via renal excretion. CONCLUSIONS:The freeze-dried bevacizumab enables convenient 99mTc radiolabeling, providing a preclinical proof-of-concept supporting further development as a tumor imaging-agent.
OBJECTIVE:To compare the clinical efficacy of the curved vertebroplasty system combined with targeted radionuclide therapy (radium-223/strontium-89) versus conventional percutaneous vertebroplasty (PVP) combined with radionuclide therapy in the treatment of malignant tumor-related pathological vertebral fractures, and to evaluate differences between the two surgical approaches in postfracture pain relief, vertebral morphological reconstruction, spinal functional recovery, and quality-of-life improvement. METHODS:A retrospective analysis was performed on 125 patients with pathologically confirmed malignant tumor bone metastasis-related pathological vertebral fractures treated between January 2022 and December 2024. All patients received targeted radionuclide therapy, and vertebroplasty was performed 14-21 d after the last radionuclide dose. Patients were divided into the curved vertebroplasty combined with radionuclide therapy group (study group, n = 63) and the conventional PVP combined with radionuclide therapy group (control group, n = 62). The primary outcome was the Visual Analogue Scale (VAS) pain score. Secondary outcomes included the postfracture vertebral height recovery rate, the Oswestry Disability Index (ODI), the Roland-Morris Disability Questionnaire (RMDQ), bone cement distribution, vertebral kyphotic angle, and SF-36 quality-of-life score. Patients were followed for 6 months, and radionuclide therapy-related adverse events were monitored. RESULTS:Baseline characteristics were comparable between the two groups (p > 0.05). At 3 and 6 months after pathological fracture surgery, VAS scores were significantly lower in the study group than in the control group (1.6 ± 0.8 vs. 2.5 ± 1.0; 1.4 ± 0.7 vs. 2.4 ± 0.9; both p < 0.01). At all postoperative time points, the study group demonstrated significantly superior vertebral height recovery rates, ODI, and RMDQ improvement (all ps < 0.017), as well as a better kyphotic angle correction (p < 0.017). The anterior-middle column bone cement fill rate was significantly higher in the study group (88.4% ± 9.1% vs. 74.6% ± 13.2%, p < 0.001), with no intraspinal cement leakage. All eight SF-36 domain scores were significantly higher in the study group at 6 months (all ps < 0.001). Hematological toxicity rates did not differ significantly between groups (14.3% vs. 12.9%, p = 0.819). CONCLUSIONS:In the surgical management of malignant tumor-related pathological vertebral fractures, the curved vertebroplasty system combined with targeted radionuclide therapy demonstrates significantly superior postfracture pain control, vertebral morphological reconstruction, spinal functional recovery, and quality-of-life improvement compared with conventional PVP combined with radionuclide therapy, without increasing radionuclide-related toxicity. The precise anterior-middle column cement filling achieved by the curved system, combined with the systemic antitumor effect of radionuclide therapy, establishes a synergistic precision treatment model of local surgical reconstruction plus systemic radionuclide therapy for tumor-related pathological vertebral fractures.
Background: Triple-negative breast cancer (TNBC) remains one of the most clinically challenging malignancies, characterized by aggressive behavior, high metastatic propensity, and limited therapeutic options. Conventional chemotherapy and immunotherapy have demonstrated only partial efficacy, underscoring the urgent need for novel precision oncology strategies. Radionuclide therapy, including targeted radioligand therapy and theranostic approaches, has emerged as a transformative modality in precision oncology, yet its application in TNBC is constrained by an incomplete understanding of molecular targets and tumor microenvironment heterogeneity. Single-cell RNA sequencing (scRNA-seq) provides unprecedented resolution for characterizing gene expression profiles and cellular heterogeneity within the TNBC ecosystem. Methods: TNBC scRNA-seq data (GSE155109) were analyzed using Scanpy for quality control, dimensionality reduction, and cluster annotation. Mendelian randomization (MR) and summary-based MR analyses were employed to identify causal associations between biomarkers, gene expression levels ( CASP8, RPS23, SLC22A5, CRIPAK, EMB, CTSW ), and TNBC risk. Module scoring quantified risk and protective gene activities across cellular compartments. UMAP (Uniform Manifold Approximation and Projection) and diffusion pseudotime analyses delineated transcriptional trajectories. Quantitative real-time PCR (qRT-PCR) in MCF10A, MDA-MB-231, and BT-549 cell lines validated key computational findings. Results: Single-cell analysis resolved 18 transcriptionally distinct clusters, reflecting the complex cellular architecture of the TNBC tumor microenvironment. Risk genes including EMB and CASP8 were preferentially expressed in endothelial-enriched cell populations, while the protective gene RPS23 was enriched in stromal compartments. Risk gene modules positively correlated with angiogenic activity, and pseudotime analysis revealed progressive risk gene activation during disease evolution. qRT-PCR confirmed significant upregulation of EMB, CASP8, CTSW, and SLC22A5 in malignant lines ( p < 0.01), with concomitant RPS23 downregulation, consistent with transcriptomic data. Collectively, these molecular landscapes define putative targets for radionuclide-based theranostic strategies in precision oncology. Conclusions: This study systematically elucidated gene expression characteristics and cellular heterogeneity in TNBC through single-cell transcriptomics, identifying key risk and protective genes with potential theranostic relevance. The identified molecular signatures represent a roadmap for developing radionuclide therapy approaches tailored to precision oncology management of TNBC.
BACKGROUND:Intratumoral heterogeneity in cervical carcinoma may influence absorbed dose distribution, treatment resistance, and response, but is not adequately captured by conventional uniform planning. METHODS:A total of 35 patients with histologically confirmed cervical carcinoma underwent baseline theranostic imaging. Voxel-wise tumor uptake was analyzed to derive SUVmax, SUVmean, tumor-to-background ratio, coefficient of variation, entropy, and fractional low-, intermediate-, and high-uptake subregions. Voxel-based absorbed dose distributions were estimated, and a dose heterogeneity index was calculated. Conventional uniform planning was compared with theranostic-guided spatial optimization. An integrated theranostic score was developed for response prediction and risk stratification. RESULTS:Nonresponders showed higher uptake intensity, greater spatial heterogeneity, larger high-uptake fractions, and higher integrated theranostic scores than responders. Tumor absorbed dose exceeded that of bladder, rectum, and normal pelvic soft tissue. SUVmean correlated positively with tumor absorbed dose, whereas uptake coefficient of variation correlated with dose heterogeneity. Theranostic-guided spatial optimization improved target coverage, conformity, and high-risk subregion coverage relative to conventional uniform planning. The integrated theranostic score demonstrated strong predictive performance for response classification (area under the receiver operating characteristic curve, 0.95; 95% confidence interval, 0.84-0.98). CONCLUSIONS:Radionuclide theranostic mapping provided a quantitative framework linking spatial uptake heterogeneity to dosimetry, planning benefit, and treatment response in cervical carcinoma.
BACKGROUND:Cervical cancer harbors a profoundly immunosuppressive tumor microenvironment (TME) that impairs innate and adaptive antitumor immunity and, critically, limits the efficacy of emerging radioimmunotherapy strategies. The NKG2D receptor-ligand axis-comprising the stress-inducible ligands MICA and MICB-constitutes a pivotal innate immune recognition interface whose surface expression on tumor cells determines susceptibility to NKG2D-armed effector cells and, by extension, dictates the targetability of radiolabeled NKG2D-directed probes for precision radionuclide therapy (RNT). Yet the mechanistic basis for NKG2D ligand dysregulation and its implications for radionuclide theranostics in cervical cancer remain poorly defined. This study integrated single-cell RNA sequencing (scRNA-seq) and experimental validation to comprehensively map the NKG2D-axis immune escape landscape in cervical carcinogenesis and to delineate its translational significance for precision RNT target selection and patient stratification. METHODS:scRNA-seq datasets (GSM1551311 and GSM1551411) were processed using Seurat and Harmony for cell-type annotation, immune landscape characterization, and radionuclide target density profiling. Louvain clustering was performed at a resolution of 0.8 after evaluating multiple resolution parameters (0.4-1.2) using the clustree package to ensure stable cluster assignments. The top 20 principal components were retained for Uniform Manifold Approximation and Projection (UMAP) embedding based on elbow plot analysis. Harmony integration used default parameters (θ = 2 and λ = 1) with convergence assessed over 20 iterations. Doublet detection was performed using DoubletFinder (v2.0.3) with an estimated doublet rate of 4.0%; additionally, cells with >40% ribosomal protein gene reads were excluded. Batch correction quality was validated using the Local Inverse Simpson's Index, Adjusted Rand Index, and silhouette coefficient metrics. Real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA) quantified expression of four candidate RNT-relevant genes-MICA, MICB (NKG2D ligands; primary radionuclide targeting molecules), SUSD1 (immunosuppressive upregulator; potential RNT resistance mediator), and STAG3L1-in HeLa, SiHa, and normal HCerEpiC cell lines. Five independent biological replicates were performed per cell line, each with three technical replicates, following Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines. Shapiro-Wilk normality testing and Levene's test for homogeneity of variance were applied prior to all parametric analyses. RESULTS:Cervical cancer scRNA-seq profiles revealed significantly depleted cluster of differentiation 8 (CD8)+ T cells (mean difference: -0.12; 95% CI: [-0.16, -0.08]; Cohen's d = 1.45) and natural killer (NK) cells (Cohen's d = 1.12), with increased CD25+ regulatory T cells (+0.08; 95% CI: [+0.05, +0.11]), establishing an RNT-unfavorable immunosuppressive TME. Comparative benchmarking against RNT-responsive tumor types, neuroendocrine tumors and prostate-specific membrane antigen (PSMA) positive prostate cancer, confirmed that cervical cancer exhibits a combination of reduced target surface density, depleted NKG2D-effector populations, and enriched immunosuppressive subsets collectively predictive of attenuated RNT efficacy. Experimental validation confirmed dramatic downregulation of MICA (HeLa: 0.44 ± 0.07 relative expression, p < 0.001, n = 5) and MICB (HeLa: 0.51 ± 0.09, p < 0.05), translating to markedly reduced MICA protein secretion (124.3 ± 18.5 pg/mL in HeLa versus 285.4 ± 31.2 pg/mL in controls, p < 0.01). Concurrently, SUSD1 was markedly upregulated (HeLa: 2.28 ± 0.25-fold; protein 3.42 ± 0.45 ng/mg, p < 0.001, n = 5). Strong mRNA-protein correlations, r = 0.78-0.92, p < 0.001; computed from five independent biological replicates per cell line; coefficient of variation (CV) < 15% for all measurements, validated transcriptomic profiling as a reliable proxy for theranostic target protein density estimation. CONCLUSIONS:This integrative study reveals that MICA/MICB downregulation and SUSD1 upregulation converge to suppress NKG2D-mediated antitumor immunity in cervical cancer, creating an immune-cold TME that limits current immunotherapy and radionuclide targeting efficacy. The NKG2D ligand expression landscape mapped here delineates a precision RNT strategy: scRNA-seq-guided patient stratification, radiolabeled anti-MICA/MICB nanobody theranostic imaging to confirm surface target density, and combination radioimmunotherapy integrating MICA/MICB re-expression induction with targeted radionuclide delivery to selectively irradiate the NKG2D-ligand-negative tumor cell population.
BACKGROUND:Type 5 insular and paralimbic gliomas are surgically challenging because resection is limited by perforator-rich vascular anatomy and eloquent subcortical pathways, often leaving clinically relevant residual disease. We evaluated a precision-oncology workflow integrating multimodal preoperative planning, transsylvian microneurosurgical resection, and postoperative radionuclide-oriented stratification. METHODS:This retrospective study included 38 adults with type 5 insular and paralimbic gliomas treated through a transsylvian approach. Structural magnetic resonance imaging (MRI), T2/fluid-attenuated inversion recovery imaging, diffusion tensor tractography, and vascular mapping were integrated to define operative corridors and safety boundaries. Early postoperative MRI was used to assess extent of resection, neurologic outcome, and residual-disease category, which was then linked to standard follow-up, radionuclide-oriented reassessment, or targeted radionuclide therapy candidacy. RESULTS:Gross total resection was achieved in 72% of patients, subtotal resection in 21%, and partial resection in 7%. No new neurologic deficit occurred in 80% of patients, transient deficits in 15%, and permanent deficits in 5%, yielding a neurologic preservation rate of 95%. Residual disease was categorized as no significant residual in 55%, surgically constrained residual in 30%, and biologically high-risk residual in 15%. CONCLUSIONS:This integrated workflow achieved high rates of maximal safe resection and neurologic preservation while providing a structured postoperative framework for biologically informed residual-disease assessment, radionuclide-oriented reassessment, and targeted radionuclide therapy candidate selection in surgically complex gliomas.
BACKGROUND:Metastatic castration-resistant prostate cancer (mCRPC) remains a therapeutic challenge, particularly in patients with suboptimal response to 177Lu-PSMA-617. Terbium-161 (Tb-161), with its emission of β-particles and high-LET Auger/conversion electrons, offers potential advantages in targeting micrometastases. However, clinical validation, especially in resource-limited settings, remains limited. MATERIALS AND METHODS:This single-center, proof-of-concept study was conducted at the Department of Nuclear Medicine, FMRI, Gurgaon. Manual in-house radiolabeling of PSMA-617 with Tb-161 was performed. The samples were withdrawn for quality control analyses. Five mCRPC patients were administered Tb-161 PSMA-617. Post-therapy planar and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging was conducted to assess biodistribution and dosimetric analysis. RESULTS:Radiolabeling PSMA-617 with Tb-161 was more than 95% efficient with 55 min of heating at 95°C. The radiochemical purity was >98% for all the runs (n = 5). The sample was found to be sterile with no gel formation seen after 15 d for all the batches. Post-therapy imaging demonstrated favorable biodistribution and high tumor uptake. Dosimetric analysis revealed absorbed doses comparable or superior to historical 177Lu-PSMA-617 data. No acute adverse events or safety concerns were observed post administration. CONCLUSIONS:This study successfully demonstrates the feasibility of manual in-house synthesis and clinical application of Tb-161 PSMA-617 in an Indian tertiary care setting. The favorable synthesis, imaging, biodistribution, and dosimetric profile support its potential as a next-generation theranostic agent for mCRPC. These findings warrant further validation through larger, controlled clinical trials.
BACKGROUND:The potential value of combining transarterial chemoembolization (TACE) with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) at intermediate-to-advanced stages remains incompletely defined. This study sought to characterize the efficacy and tolerability of this combined approach and to delineate pretreatment characteristics linked to patient prognosis. METHODS:A retrospective analysis was conducted on 248 consecutive HCC patients managed between January 2020 and December 2024. Treatment allocation at the time of initial decision resulted in 126 patients receiving TACE in conjunction with ICIs, whereas 122 were managed with TACE as the sole intervention. Radiological response was independently adjudicated according to the modified Response Evaluation Criteria in Solid Tumors. Survival endpoints-namely progression-free survival (PFS) and overall survival (OS)-were derived via the Kaplan-Meier methodology, with prognostic determinants explored through Cox regression modeling. RESULTS:The addition of ICIs to TACE conferred a substantially higher objective response rate (46.0% vs. 24.6%, p < 0.001) and disease control rate (77.8% vs. 59.8%, p = 0.003). The combination arm demonstrated a median PFS of 10.8 months, compared with 5.6 months in patients receiving TACE alone (p < 0.001); corresponding median OS figures were 21.6 and 14.2 months (p < 0.001). On multivariate Cox analysis, an Eastern Cooperative Oncology Group (ECOG) performance status of 2, serum α-fetoprotein (AFP) ≥400 ng/mL, portal vein tumor thrombus (PVTT), extrahepatic disease extension, and a neutrophil-to-lymphocyte ratio ≥5 each emerged as independent predictors of inferior PFS. Shorter OS was independently linked to ECOG 2, Child-Pugh class B, elevated AFP, PVTT, and distant metastases. Across both endpoints, the combination strategy retained independent prognostic significance (both p < 0.001). Serious immune-mediated toxicity (grades 3 and 4) was recorded in 15.1% of patients; 9.5% required permanent ICI discontinuation, and no fatality attributable to treatment was observed. CONCLUSIONS:In this real-world retrospective series, the integration of ICIs into TACE-based treatment was associated with meaningful gains in tumor response and survival among patients with intermediate-to-advanced HCC, without generating unacceptable safety signals. Stratification by functional status, hepatic functional reserve, AFP burden, vascular invasion, metastatic spread, and inflammatory markers may enhance individualized prognostic assessment in this population.
OBJECTIVE:To investigate the effects of perioperative 177Lutetium (177Lu)-labeled anticarcinoembryonic antigen (CEA)-targeted radionuclide therapy (TRT) on perioperative inflammatory response, intestinal function recovery, pain control, dosimetric safety, and postoperative complications in colorectal cancer surgery patients within a precision oncology framework. METHODS:A retrospective analysis of 72 patients who underwent elective radical colorectal cancer surgery (January 2022-December 2023). Patients were divided into a TRT group and a control group (36 cases each). The TRT group received 177Lu-labetuzumab (1.85 GBq) 48 h preoperatively and a consolidation dose (0.74 GBq) at 24 h postoperatively; the control group received equivalent saline. Perioperative inflammatory markers [C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), white blood cell, neutrophil percentage], intestinal function recovery, visual analogue scale (VAS) pain scores, analgesic medication usage, dosimetric parameters, nutritional indicators, and postoperative complications were compared. RESULTS:Baseline characteristics were comparable between groups (p > 0.05). Compared with the control group, the TRT group showed significantly lower inflammatory markers on postoperative days 3 and 7 (p < 0.05), shorter bowel sound recovery time (18.4 ± 6.7 h vs. 26.8 ± 8.9 h), first flatus time (28.6 ± 9.3 h vs. 42.1 ± 12.7 h), and defecation time (58.7 ± 18.4 h vs. 78.9 ± 22.6 h) (p < 0.001). VAS scores at all time points were significantly lower (p < 0.001), with reduced analgesic consumption. Tumor-absorbed dose was 32.7 ± 8.4 Gy with critical organ doses within International Commission on Radiological Protection tolerance. No serious radiotoxic adverse reactions occurred. CONCLUSIONS:In this retrospective exploratory study of imaging-selected colorectal cancer patients, perioperative 177Lu-labeled anti-CEA TRT was associated with lower postoperative inflammatory marker levels, faster recovery of intestinal function, reduced analgesic requirements, and an acceptable short-term safety profile. These findings suggest that perioperative TRT may have potential short-term benefits in carefully selected patients, but prospective studies are required before broader clinical adoption.
Purpose: Targeted radionuclide therapy with 177Lu-PSMA-617 prolongs radiographical progression-free survival in prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC), yet 13% of patients develop symptomatic skeletal events. The authors hypothesized that hemoglobin-based oxygen carriers (HBOCs) could potentiate 177Lu-PSMA-617 by reprogramming bone marrow (BM) immunity.Methods:Using PSMA-expressing xenografts, they demonstrated that concomitant HBOC administration significantly reduced tumor volume without increasing systemic toxicity. To dissect the underlying mechanism, the authors performed high-resolution single-cell RNA sequencing of murine BM.Results:HBOC treatment markedly expanded mature neutrophils, plasmacytoid dendritic cells, classical monocytes, natural killer T cells, and mature B cells, while concomitantly upregulating DNA damage repair genes such as Parp9, Dtx3l, and Smchd1 within these subsets. Gene set enrichment analysis confirmed significant activation of DNA damage response pathways, implying enhanced cellular radioresistance and improved tolerance to β-particle irradiation.Conclusions: Thus, HBOCs improve 177Lu-PSMA-617 antitumor efficacy indirectly via immune-subset expansion and DNA-repair reinforcement, offering a clinically feasible and safe strategy to optimize combination protocols for patients with mCRPC.
BACKGROUND: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. MATERIALS AND METHODS: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. RESULTS: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. CONCLUSIONS: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.
OBJECTIVE:To ascertain whether cavitation-free acoustic sensitization enhances intracellular delivery and amplifies polo-like kinase 4 (PLK4)-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. METHODS: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 in vitro models. The cell counting kit-8 test was used to measure cell proliferation, proliferating cell nuclear antigen (PCNA) 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 PLK4 and downstream tumor protein 53 (p53)-cyclin-dependent kinase inhibitor 1A (p21) signaling components. To verify pathway specificity, PLK4 overexpression studies were carried out. A nude mouse xenograft model was used to evaluate in vivo antitumor effectiveness and biosafety. RESULTS: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 PCNA and PLK4 expression and activation of the p53-p21 tumor suppressor pathway. The anticancer effects of DE02 and ExoDE02 were successfully inhibited by overexpression of PLK4, indicating PLK4-dependent therapeutic efficacy. ExoDE02 significantly inhibited the growth of xenograft tumors in vivo, decreased tumor weight and volume, and showed no discernible systemic toxicity. CONCLUSIONS:By increasing the therapeutic efficacy of the phillyrin derivative DE02 via a safe, nondestructive exosome-based delivery method, cavitation-free acoustic sensitization improves PLK4-targeted osteosarcoma therapy. For targeted osteosarcoma biotherapy, this ultrasound-enabled method provides a mechanistically defined and physiologically applicable platform.
OBJECTIVE:To investigate the treatment response status in elderly patients with metastatic castration-resistant prostate cancer (mCRPC) receiving 177Lu-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. METHODS:A cross-sectional survey study was conducted, including 182 elderly patients (age ≥65 years, having completed ≥2 cycles of 177Lu-PSMA-617 therapy) with prostate-specific membrane antigen (PSMA)-positive mCRPC confirmed by 68Ga-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. RESULTS: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, p < 0.001) and lower anxiety, depression, and pain scores compared with the nonresponse group. Multivariate analysis identified baseline hemoglobin < 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 < 12 (OR = 2.39, 95% CI: 1.11-5.14), and baseline alkaline phosphatase (ALP) > 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 (χ2trend = 5.214, p = 0.022). CONCLUSIONS:Elderly mCRPC patients undergoing 177Lu-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 strategies for 177Lu-PSMA-617 therapy.
Background: 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. Methods: 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. Results: 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%, p < 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. Conclusions: 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.
