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13 pages, 6846 KB  
Article
Initial Experience with Dual-Tracer Sentinel Lymph Node Mapping Using RI and ICG in Robot-Assisted Surgery for Early-Stage Endometrial Cancer: A Prospective Exploratory Study
by Masayo Okawa, Hiroaki Komatsu, Yuki Hiratsuka, Koji Yamamoto, Kohei Hikino, Yuki Iida, Mayumi Sawada, Shinya Sato and Fuminori Taniguchi
J. Clin. Med. 2026, 15(12), 4705; https://doi.org/10.3390/jcm15124705 - 17 Jun 2026
Viewed by 126
Abstract
Background/Objectives: Sentinel lymph node (SLN) biopsy is a minimally invasive alternative to systematic lymphadenectomy for endometrial cancer staging. However, optimization of SLN identification during robot-assisted surgery remains an important clinical issue. This prospective exploratory study evaluated the feasibility and mapping characteristics of dual-tracer [...] Read more.
Background/Objectives: Sentinel lymph node (SLN) biopsy is a minimally invasive alternative to systematic lymphadenectomy for endometrial cancer staging. However, optimization of SLN identification during robot-assisted surgery remains an important clinical issue. This prospective exploratory study evaluated the feasibility and mapping characteristics of dual-tracer SLN mapping combining radioisotope (RI) and indocyanine green (ICG) in robot-assisted surgery for clinical stage IA endometrial cancer. Methods: Ten patients with clinical stage IA endometrioid carcinoma (grade 1 or 2) who underwent robot-assisted surgery at our institution between June 2025 and March 2026 were prospectively enrolled. Technetium-99m phytate was injected cervically the day before surgery, followed by SPECT-CT imaging. ICG was administered intraoperatively. SLNs were identified using both RI mapping and near-infrared fluorescence imaging. All patients subsequently underwent pelvic lymphadenectomy. SLN detection rates, concordance between tracers, intraoperative findings, and perioperative outcomes were evaluated. Results: The SLN detection rate with the dual-tracer method was 100% (10/10). RI mapping alone achieved bilateral detection in 30% (3/10), whereas ICG fluorescence imaging identified SLNs in all patients (100%). All RI-positive SLNs were also identified by ICG fluorescence imaging. In several cases, multiple fluorescent lymph nodes were observed, and gamma-probe assessment aided intraoperative SLN selection. No lymph node metastases were identified. One Clavien–Dindo grade IIIa complication (pelvic hematoma requiring intervention) occurred. No adverse events related to ICG were observed. Conclusions: Dual-tracer SLN mapping using RI and ICG was feasible in robot-assisted surgery for clinical stage IA endometrial cancer. ICG fluorescence imaging provided sensitive lymphatic visualization, whereas RI mapping offered complementary information for intraoperative SLN identification in selected cases. Further prospective studies with larger cohorts are required to clarify the clinical utility of the dual-tracer approach. Full article
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15 pages, 1036 KB  
Article
Is There an Added Value of Dual-Time-Point [68Ga]Ga–Fibroblast Activation Protein Inhibitor (FAPI) PET/CT in Differentiating Malignant and Benign Uptake Findings?
by Akram Al-Ibraheem, Serin Moghrabi, Baraa Alsyouf, Marwah Abdulrahman, Mahd Al-Foqaha, Farah Al-Tameemi, Bara’ah Bashabsheh, Saad Ruzzeh, Dimah Khalid Jiad, Ahmed Firas Al-Hammouri, Hongcheng Shi, Ahmed Saad Abdlkadir and Asem Mansour
Cancers 2026, 18(12), 1963; https://doi.org/10.3390/cancers18121963 - 17 Jun 2026
Viewed by 173
Abstract
Background: [68Ga]Ga-FAPI PET/CT demonstrates high sensitivity for tumor detection but limited specificity because benign fibro-inflammatory conditions may also show tracer uptake. Dual-time-point imaging has been proposed to improve lesion characterization by assessing temporal changes in uptake. This study evaluated whether [...] Read more.
Background: [68Ga]Ga-FAPI PET/CT demonstrates high sensitivity for tumor detection but limited specificity because benign fibro-inflammatory conditions may also show tracer uptake. Dual-time-point imaging has been proposed to improve lesion characterization by assessing temporal changes in uptake. This study evaluated whether delayed imaging provides incremental diagnostic value over standard early imaging. Methods: This retrospective lesion-based study evaluated dual-time-point [68Ga]Ga-FAPI PET/CT imaging. SUVmax, maximal tumor-to-background ratio (TBRmax), metabolic tumor volume (MTV), and total lesion uptake (TLU) were measured on early and delayed scans. Diagnostic performance for differentiating malignant from benign uptake findings was assessed using receiver operating characteristic analysis. Results: A total of 123 patients underwent dual-time-point imaging at approximately 26 and 65 min post-injection. Overall, 620 [68Ga]Ga-FAPI uptake findings were analyzed, including 307 malignant uptake findings and 313 benign findings. SUVmax decreased significantly over time in both malignant and benign uptake findings, with a greater decline in benign findings (%ΔSUVmax −7.7% vs. −3.6%, p = 0.0045). TBRmax increased modestly in malignant uptake findings, while MTV and TLU remained largely stable. SUVmax and TBRmax were significantly higher in malignant uptake at both imaging time points; however, diagnostic performance remained moderate (AUCs of 0.65–0.69) due to substantial overlap between lesion types. Delayed imaging did not improve diagnostic accuracy compared with early imaging, and delta parameters demonstrated poor performance (AUC ~0.5). Similar findings were observed across tumor subgroups. Conclusions: In this lesion-based retrospective cohort, delayed dual-time-point [68Ga]Ga-FAPI PET/CT did not demonstrate meaningful incremental diagnostic value over early imaging. A standard early acquisition appears adequate for routine practice, although lesion interpretation remains dependent on clinical, morphologic, and, when needed, histopathologic correlation. Full article
(This article belongs to the Special Issue Advances in PET/CT Imaging in Cancer Management)
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17 pages, 1911 KB  
Article
3D Bioprinting of an Oral Colon Delivery System for Precision Bacteriotherapy
by Alessandra Buscarini, Saliha Moutaharrik, Gabriele Meroni, Matteo Cerea, Martina Edith Coldani, Anastasia Foppoli, Luca Palugan, Andrea Gazzaniga, Piera Anna Martino and Alessandra Maroni
Pharmaceutics 2026, 18(6), 735; https://doi.org/10.3390/pharmaceutics18060735 - 13 Jun 2026
Viewed by 374
Abstract
Objectives: A customizable 3D-bioprinted core-in-shell platform was developed for time-dependent oral colon delivery of live microorganisms. The system conveyed Lacticaseibacillus paracasei as a model bacterial species within a monolithic core, which was surrounded by a swellable hydroxypropyl cellulose barrier, imparting a lag phase [...] Read more.
Objectives: A customizable 3D-bioprinted core-in-shell platform was developed for time-dependent oral colon delivery of live microorganisms. The system conveyed Lacticaseibacillus paracasei as a model bacterial species within a monolithic core, which was surrounded by a swellable hydroxypropyl cellulose barrier, imparting a lag phase of programmable duration, and by an enteric outer layer, protecting the dosage form during unpredictable gastric residence. Methods: Pastes of different compositions were investigated to shape the core. Core and core-in-shell units were fabricated from digital models using a bioprinter equipped with a high-precision plunger dispenser and pressure-based thermoplastic printhead. The printed units were characterized in terms of mass, dimensions, mechanical properties and release performance using paracetamol as a reference tracer. Bacterial viability was evaluated during screening of the formulation components and after each processing step by manual counting of colony-forming units. Results: A mannitol-based formulation was selected for fabrication of the core, offering a favorable balance of printability, physico-technological properties, release behavior and ability to preserve bacterial viability. Two-layer core-in-shell systems were manufactured via a dual-printing operating mode. The desired in vitro performance was attained, with no release under acidic conditions, a lag phase in pH 6.8 fluid and a subsequent release profile comparable with that generated by the core as such. Viability studies demonstrated that compounding, core printing, shell deposition and drying did not adversely affect L. paracasei survival. Conclusions: 3D bioprinting was proved to be a versatile technique for the manufacturing of oral colon delivery systems containing probiotics or live biotherapeutics. Full article
(This article belongs to the Special Issue 3D Printing in Personalized Drug Delivery)
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16 pages, 11652 KB  
Article
Decoding the Myocardium: Tracer-Aware Deep Learning for Patient-Level Classification in Stress–Rest SPECT Myocardial Perfusion Imaging
by Dimitrios Samaras, Dimitra Tsivaka, Maria Vakalopoulou, Panagiotis Papadimitroulas, George Angelidis, Thomas Kilindris, Varvara Valotassiou, Dimitrios Psimadas, Emmanouil Panagiotidis, Panagiotis Georgoulias and Ioannis Tsougos
Diagnostics 2026, 16(12), 1796; https://doi.org/10.3390/diagnostics16121796 - 10 Jun 2026
Viewed by 213
Abstract
Background/Objectives: Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is widely used for non-invasive assessment of coronary artery disease under stress and rest conditions. Although deep learning has shown promise for automated SPECT MPI interpretation, most studies focus on single-tracer datasets and [...] Read more.
Background/Objectives: Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is widely used for non-invasive assessment of coronary artery disease under stress and rest conditions. Although deep learning has shown promise for automated SPECT MPI interpretation, most studies focus on single-tracer datasets and do not explicitly account for tracer-dependent variability. This study developed and evaluated a multi-task deep learning framework with tracer-specific prediction heads for patient-level SPECT MPI classification. Methods: A convolutional neural network with a shared feature encoder and tracer-specific heads was implemented using polar map representations from technetium-99m (Tc-99m) and thallium-201 (Tl-201) studies. Transfer learning from ImageNet was applied. Stress-only, rest-only, and dual-input configurations were evaluated using repeated patient-stratified cross-validation and independent testing. Performance was assessed using ROC-AUC and balanced accuracy. Results: For Tc-99m normal versus abnormal perfusion classification, the stress-only model achieved the highest cross-validation AUC (0.88 ± 0.067) and test AUC of 0.88 [0.67–0.99]. For Tl-201 low-risk versus intermediate/high-risk classification, stress-based models achieved the highest cross-validation AUC (0.88 ± 0.051) and test AUC of 0.80 [0.71–0.89], comparable to dual-input models. In both tracer-specific tasks, stress-phase information showed favorable performance, but the endpoints differed and should be interpreted separately. Conclusions: Stress-phase polar maps provided strong discriminative information within this single-center cohort. These findings should be interpreted in a tracer- and task-specific manner supporting stress-phase imaging as an informative input for AI-based SPECT MPI classification while underscoring the need for external validation before broader clinical generalization. Full article
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25 pages, 3163 KB  
Article
Fracturing Tracer Monitoring and Machine Learning-Assisted Geology-Engineering Coupled Optimization for Deep Coalbed Methane Horizontal Wells
by Hong Zhuo, Zhangying Han, Shaohua Li, Xiuling He, Demei Zhang, Haibin Song and Gang Hui
Processes 2026, 14(12), 1890; https://doi.org/10.3390/pr14121890 - 10 Jun 2026
Viewed by 119
Abstract
Evaluating the productivity contribution of individual fracturing stages in deep coalbed methane (CBM) horizontal wells remains a critical challenge, hindering the optimization of stimulation designs. This study systematically integrates dual-phase (aqueous and gaseous) fracturing tracer monitoring with machine learning algorithms to address this [...] Read more.
Evaluating the productivity contribution of individual fracturing stages in deep coalbed methane (CBM) horizontal wells remains a critical challenge, hindering the optimization of stimulation designs. This study systematically integrates dual-phase (aqueous and gaseous) fracturing tracer monitoring with machine learning algorithms to address this issue. Based on large-scale field applications across ten deep CBM horizontal wells in the Changqing mining area of the Ordos Basin, comprising 132 monitored stages, quantitative production profile data were interpreted. Three distinct gas production archetypes—Homogeneous, Heel-Dominated, and Heterogeneous—were identified, each governed by specific geomechanical and stratigraphic controls. Pearson correlation analysis and Random Forest feature importance ranking were employed to decouple the hierarchical influence of geological parameters (Class I coal intersection length, trajectory position, coal thickness) and engineering parameters (proppant volume, pumping rate, fluid volume). A power-law correlation between Class I coal length and initial gas productivity was quantified (R2 = 0.71). For the first time, an economically viable “differentiated fracturing scale window” tailored to coal petrophysical classes and wellbore trajectory positions was defined. Subsequently, a machine learning-assisted geology-engineering closed-loop optimization methodology was established, using tracer data as a dynamic feedback bridge to iteratively refine fracturing designs. This research provides a reliable technical approach and practical template for enhancing single-well productivity and recovery efficiency in deep unconventional gas reservoirs. Full article
(This article belongs to the Section AI-Enabled Process Engineering)
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43 pages, 7855 KB  
Review
Advances in GPCR-Targeted PET Radiotracer Patents (2020–2025)
by Rebecca Ferrisi, Clara Mocchetti, Alessia Cazzaniga, Marco De Amici, Claudio Papotto and Clelia Dallanoce
Pharmaceuticals 2026, 19(6), 900; https://doi.org/10.3390/ph19060900 - 5 Jun 2026
Viewed by 251
Abstract
Background: Positron emission tomography (PET) is a molecular imaging technique that exploits the β+ decay of selected radionuclides to enable non-invasive in vivo investigation of biochemical and physiological processes, including early and subclinical disease alterations. Radiotracers are designed to bind specific molecular [...] Read more.
Background: Positron emission tomography (PET) is a molecular imaging technique that exploits the β+ decay of selected radionuclides to enable non-invasive in vivo investigation of biochemical and physiological processes, including early and subclinical disease alterations. Radiotracers are designed to bind specific molecular targets with high affinity and selectivity. Among the targets to which PET devotes increasing attention are G protein-coupled receptors (GPCRs)—the largest class of transmembrane receptors—which orchestrate a wide spectrum of biological outcomes and are widely implicated in human disease. Objectives: This review analyzes patents published between 2020 and 2025 focusing on GPCR-targeted PET radiotracers, highlighting design strategies, radionuclide selection, and translational perspectives across oncology, central nervous system (CNS) disorders, and inflammatory diseases. Results: Patent activity shows that most GPCR-targeted PET tracers are derived from validated ligands adapted for imaging while preserving affinity and selectivity. Oncology patents mainly favor peptide-based or modular metal–chelator platforms enabling radionuclide flexibility and theranostic extension, whereas CNS tracers rely on drug-like small molecules optimized under strict ADME and blood–brain barrier constraints. Increasing emphasis on non-orthosteric, function-sensitive, and dual-targeting approaches reflects a shift toward interrogating GPCR signaling states, while inflammatory indications remain comparatively underrepresented despite clear biological foundations. Conclusions: Current patent trends consolidate GPCR-targeted PET tracers as well-established diagnostic tools while progressively expanding their clinical utility, both as platforms supporting translational research—informing mechanistic insight and drug development—and as components of emerging theranostic strategies across multiple disease areas. Full article
(This article belongs to the Special Issue Development of Novel Radiopharmaceuticals for SPECT and PET Imaging)
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13 pages, 1293 KB  
Article
Comparison of Indocyanine Green Fluorescence and Technetium-99m for Sentinel Lymph Node Detection in Breast Cancer: A Retrospective Single-Center Study
by Alexandra Nienhaus, Ann-Kathrin Waning, Lena Rotering and Elena Silvia Bernad
Diagnostics 2026, 16(11), 1743; https://doi.org/10.3390/diagnostics16111743 - 5 Jun 2026
Viewed by 237
Abstract
Background/Objectives: Sentinel lymph node biopsy (SLNB) is the standard procedure for axillary staging in early breast cancer. While technetium-99m (99mTc) radiocolloid is currently the standard tracer, indocyanine green (ICG) fluorescence represents a promising alternative. This study aimed to compare the detection [...] Read more.
Background/Objectives: Sentinel lymph node biopsy (SLNB) is the standard procedure for axillary staging in early breast cancer. While technetium-99m (99mTc) radiocolloid is currently the standard tracer, indocyanine green (ICG) fluorescence represents a promising alternative. This study aimed to compare the detection rates of both methods in a dual-tracer setting. Methods: A retrospective, single-center cohort study was conducted at the Department of Gynecology, Ahaus Hospital, Germany, between April 2024 and March 2025. Fifty-two patients with malignant breast tumors underwent SLNB using both ICG fluorescence and 99mTc radiocolloid. Results: Combined tracer use achieved a 100% sentinel lymph node detection rate. ICG alone detected nodes in 49/52 patients (94.23%), while 99mTc achieved detection in 50/52 patients (96.15%). ICG identified all eight metastatic cases (100%), whereas 99mTc identified seven of eight (87.5%). In obese patients (BMI ≥ 30, n = 10), ICG achieved 100% detection versus 90% for 99mTc. The cost per application was 62.73 EUR for ICG versus approximately 250 EUR for 99mTc. Conclusions: ICG fluorescence demonstrates comparable detection rates to 99mTc with advantages in cost-effectiveness, feasibility, and performance in obese patients. ICG represents a safe, radiation-free alternative for sentinel lymph node mapping in breast cancer surgery. Full article
(This article belongs to the Special Issue Advanced Diagnostics in Women's Health: From Biomarkers to Imaging)
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14 pages, 1423 KB  
Case Report
Extraosseous 99mTc-MDP Uptake Guiding Intraoperative Sampling in Severe Inflammatory Myopathy: A Case Report and Literature Review
by Masha Maharaj, Sanvir Sirriram, Nav Govender, Trisha Govender, Babita D. Bhana and Nisaar Korowlay
Diagnostics 2026, 16(11), 1684; https://doi.org/10.3390/diagnostics16111684 - 29 May 2026
Viewed by 395
Abstract
Background/Objectives: We report a case of severe dermatomyositis demonstrating characteristic widespread extraosseous uptake on 99mTc-methylene diphosphonate (99mTc-MDP) bone scintigraphy. This study highlights the diagnostic value of this modality in detecting active inflammatory myopathy when conventional muscle biopsy is inconclusive and [...] Read more.
Background/Objectives: We report a case of severe dermatomyositis demonstrating characteristic widespread extraosseous uptake on 99mTc-methylene diphosphonate (99mTc-MDP) bone scintigraphy. This study highlights the diagnostic value of this modality in detecting active inflammatory myopathy when conventional muscle biopsy is inconclusive and introduces its novel use for intraoperative gamma-probe-guided biopsy to precisely target metabolically active muscle. This approach may help target metabolically active muscle in heterogeneous idiopathic inflammatory myopathies (IIMs). Case Presentation: A 49-year-old man developed progressive proximal muscle weakness (Medical Research Council grade 2/5 proximally, 5/5 distally) beginning in June 2025 following influenza infection, accompanied by dysphagia, classic dermatomyositis cutaneous manifestations, back pain, and difficulty standing. Laboratory evaluation revealed elevated inflammatory markers (ESR 55 mm/hr, CRP 20 mg/L), leukocytosis (16.58 × 109/L), markedly raised creatine kinase (19,937 IU/L), and troponin T levels. An initial quadriceps muscle biopsy performed on 29 July 2025 was non-diagnostic. Three-phase 99mTc-MDP scintigraphy (~1110 MBq) demonstrated intense, diffuse extraosseous uptake involving bilateral deltoids (symmetric), biceps and triceps (patchy), paraspinal muscles (longitudinal), gluteal muscles, thighs (quadriceps and hamstrings), and gastrocnemius muscles, with relative suppression of appendicular skeletal uptake on delayed images due to soft-tissue tracer dominance—findings consistent with severe inflammatory myopathy. Following reinjection (~1100 MBq), intraoperative gamma-probe-guided biopsy targeted areas of highest uptake (left quadriceps femoris and distal triceps brachii; intraoperative counts 1300–1400 versus background ~500). Histopathology revealed histiocyte-predominant inflammation with myofibre necrosis and regeneration, sparse CD4+ T-cell infiltrates, and absence of fibrosis, consistent with necrotising myopathy. Positive antinuclear antibodies and strong anti-Mi-2 antibodies confirmed the diagnosis of dermatomyositis. Treatment included pulse methylprednisolone followed by oral prednisone taper, methotrexate, azathioprine, intravenous immunoglobulin, and planned rituximab therapy. Discussion: Whole-body 99mTc-MDP scintigraphy provided a complementary whole-body functional assessment of disease extent, revealing widespread muscular involvement. The novel application of intraoperative gamma-probe-guided biopsy enabled real-time targeting of metabolically active muscle, facilitating targeted sampling after an initial non-diagnostic biopsy and yielding supportive histopathological findings. This dual diagnostic and interventional role demonstrates the technical feasibility of gamma-probe guidance in a diagnostically challenging case of dermatomyositis. Conclusions: In our case, the integration of 99mTc-MDP scintigraphy with gamma-probe-guided biopsy enabled precise targeting of metabolically active muscle following an initial non-diagnostic biopsy. This multimodal approach may be useful in selected diagnostically challenging cases of severe inflammatory myopathy. Larger studies are needed to evaluate its reproducibility and added value. Full article
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28 pages, 1604 KB  
Review
Deciphering the Heterogeneity of Cancer-Associated Fibroblasts in Prostate Cancer: From Stromal Biology to Clinical Translation
by Ho Trong Tan Truong, Whi-An Kwon, Hyeong Jung Woo, Minseok S. Kim, Nhu Quang Tran and Jae Young Joung
Cancers 2026, 18(10), 1600; https://doi.org/10.3390/cancers18101600 - 14 May 2026
Viewed by 413
Abstract
Prostate cancer (PCa) progression and treatment resistance are driven by tumor-intrinsic mechanisms and adaptive remodeling of the tumor microenvironment, in which cancer-associated fibroblasts (CAFs) play a crucial role. Although CAF biology is increasingly recognized, a major translational gap remains: CAFs are highly heterogeneous, [...] Read more.
Prostate cancer (PCa) progression and treatment resistance are driven by tumor-intrinsic mechanisms and adaptive remodeling of the tumor microenvironment, in which cancer-associated fibroblasts (CAFs) play a crucial role. Although CAF biology is increasingly recognized, a major translational gap remains: CAFs are highly heterogeneous, and comprise distinct functional states with divergent effects on disease progression, immune regulation, and therapeutic resistance. To bridge this gap, we synthesize evidence from single-cell and spatial transcriptomic studies, tissue-based pathology, liquid biopsy assays, and molecular imaging to construct an evidence-tiered, decision-oriented translational framework that connects stromal mechanisms, translational measurement strategies, and therapeutic interventions in PCa. Single-cell and spatial transcriptomic analyses have consistently identified multiple CAF programs, including matrix-remodeling, inflammatory, immunoregulatory, antigen-presenting, and therapy-imprinted states, each with distinct functional outputs and clinical correlates. Tissue-based readouts, including reactive stromal grade (RSG) and fibroblast activation protein (FAP) immunohistochemistry, provide practical proxies for stromal activation and correlate with disease-specific mortality and imaging phenotypes. Circulating CAFs (cCAFs) represent an emerging liquid biopsy modality for longitudinal stromal monitoring, although technical standardization is required before clinical implementation. FAP-targeted PET imaging and emerging dual prostate-specific membrane antigen (PSMA)/FAP-targeted theranostic strategies provide noninvasive tools for patient selection and response assessment, particularly in PSMA-discordant or tracer-heterogeneous disease. Androgen receptor (AR)-targeted therapy can reprogram stromal states toward resistance-promoting circuits, highlighting the dynamic and plastic nature of the CAF compartment. A state-based CAF framework organizes stromal biology into testable translational hypotheses rather than immediate clinical standards. RSG and FAP-based tissue or imaging readouts are practical markers of stromal activation, whereas spatial CAF-immune signatures and cCAF assays remain investigational and require assay harmonization and prospective validation. Future trials should pre-specify stromal biomarkers as enrichment or pharmacodynamic variables when matched to the intervention and should avoid treating CAFs as a uniform therapeutic target. Full article
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12 pages, 1866 KB  
Article
Prognostic Value of 18F-FDG and 18F-FEC Uptake in Hepatocellular Carcinoma Using Contrast-Enhanced Integrated PET/MRI: Correlation with Histology and Survival
by Marzieh Nejabat, Lucian Beer, Theresa Servus, Ahmed Ba-Ssalamah, Peter Mazal, Lukas Nics, Marcus Hacker, Georgios Karanikas and Sazan Rasul
Cancers 2026, 18(10), 1526; https://doi.org/10.3390/cancers18101526 - 9 May 2026
Viewed by 577
Abstract
Background: Dual-tracer positron emission tomography/magnetic resonance imaging (PET/MRI) using [18F]-fluorodeoxyglucose (18F-FDG) and [18F]-fluoroethylcholine (18F-FEC) may reveal complementary aspects of hepatocellular carcinoma (HCC) biology. This retrospective study evaluates whether PET parameters obtained from 18F-FDG and [...] Read more.
Background: Dual-tracer positron emission tomography/magnetic resonance imaging (PET/MRI) using [18F]-fluorodeoxyglucose (18F-FDG) and [18F]-fluoroethylcholine (18F-FEC) may reveal complementary aspects of hepatocellular carcinoma (HCC) biology. This retrospective study evaluates whether PET parameters obtained from 18F-FDG and 18F-FEC correlate with MRI enhancement parameters, tumor histological grade, and survival in patients with HCC. Methods: We retrospectively evaluated 25 patients who underwent integrated PET/MRI. Lesions were analyzed on pre-contrast MRI and at early (3–5 min) and late (20–30 min) post-contrast phases. For 18F-FDG and 18F-FEC, standardized uptake values (SUV maximum, mean, and peak) and metabolic tumor volume were measured, along with lesion size, MRI enhancement ratios, AFP levels, and survival. For patient-level imaging analyses, the largest lesion per patient was defined as the index lesion. Correlation analysis using Spearman’s rank correlation coefficient, Kaplan–Meier analysis, log-rank testing, and exploratory Cox proportional hazards models were performed. Results:18F-FDG SUVmean (index lesion) showed the strongest inverse association with survival (r = −0.61, p = 0.003), followed by SUVpeak (r = −0.50, p = 0.012). 18F-FDG SUVmean differed across tumor grades (G1–G3; p = 0.040), without a consistent trend. In Cox regression, 18F-FDG SUVpeak was significantly associated with shorter overall survival (HR 1.22, 95% CI 1.05–1.42, p = 0.01), whereas SUVmean showed only a borderline association (p = 0.07). When split at the median, SUVmean was also significantly associated with shorter survival (p < 0.001; HR 10.39, 95% CI 2.75–39.3). 18F-FEC parameters were not associated with survival but showed a moderate correlation with AFP levels (r = 0.41, p = 0.01). Dynamic MRI early and delayed enhancement of the index lesion were strongly correlated (r = 0.70, p < 0.001) but not associated with survival. Conclusions: In HCC, 18F-FDG uptake provides prognostic information beyond MRI enhancement and histology, reflecting tumor aggressiveness and independently predicting survival. While 18F-FEC-PET complements lesion characterization and correlates with AFP, it does not show meaningful prognostic value. MRI enhancement parameters were not associated with survival in this cohort. 18F-FDG-based metabolic imaging may improve pre-treatment risk stratification, whereas dual-tracer PET/MRI should be considered a selective, exploratory approach rather than routine imaging. Full article
(This article belongs to the Section Methods and Technologies Development)
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15 pages, 1126 KB  
Article
Beyond Binary Positivity: Spectrum of Nodal Tumor Burden in Sentinel Lymph Node Biopsy for High-Risk Cutaneous Squamous Cell Carcinoma
by Irena Janković, Goran Stevanović, Toma Kovačević, Dimitrije Janković and Dimitrije Pavlović
Dermatopathology 2026, 13(2), 20; https://doi.org/10.3390/dermatopathology13020020 - 30 Apr 2026
Viewed by 516
Abstract
Background and Objectives: Sentinel lymph node biopsy (SLNB) is increasingly used for high-risk, clinically node-negative cutaneous squamous cell carcinoma (cSCC), yet pathological reporting remains binary, lacking morphological stratification. The prognostic relevance of nodal tumor burden subtypes—isolated tumor cells (ITC), micrometastases, and macrometastases—is [...] Read more.
Background and Objectives: Sentinel lymph node biopsy (SLNB) is increasingly used for high-risk, clinically node-negative cutaneous squamous cell carcinoma (cSCC), yet pathological reporting remains binary, lacking morphological stratification. The prognostic relevance of nodal tumor burden subtypes—isolated tumor cells (ITC), micrometastases, and macrometastases—is well established in melanoma and breast cancer but remains uncharacterized in cSCC. We aimed to describe the morphological spectrum of sentinel lymph node involvement in a consecutive institutional cohort and determine whether primary tumor characteristics predict the extent of nodal colonization. Materials and Methods: We conducted a retrospective-observational study at Clinical Center Niš (Serbia) including 35 consecutive clinically N0 high-risk cSCC patients who underwent SLNB using a dual-tracer protocol (99mTc-labeled albumin and methylene blue). Sentinel nodes were processed by serial sectioning with hematoxylin-eosin and pancytokeratin (AE1/AE3) immunohistochemistry. Deposits were classified as ITC (≤0.2 mm), micrometastases (>0.2–2.0 mm), or macrometastases (>2.0 mm). Clinicopathologic predictors were evaluated using the Mann–Whitney U test, Fisher’s exact test, the Kruskal–Wallis test, and the Spearman rank correlation test. Results: SLN involvement was identified in 12 of 35 patients (34.3%). Among positive cases, ITC accounted for 6 patients (50.0%), micrometastases for 5 (41.7%), and macrometastasis for 1 (8.3%)—minimal nodal disease constituting 91.7% of positive findings. No primary tumor feature—including diameter, thickness, grade, perineural invasion, or lesion multiplicity—significantly distinguished ITC from overt metastatic deposits. Patients with ITC showed numerically higher median tumor thickness (8.0 mm) than those with micrometastases (4.0 mm), though this did not reach significance (Kruskal–Wallis p = 0.065). Conclusions: SLN positivity in high-risk cSCC is morphologically heterogeneous, with minimal nodal disease predominating. Primary tumor features do not reliably stratify the extent of nodal colonization. Structured tumor-burden reporting—distinguishing ITC, micrometastases, and macrometastases—should be adopted as standard practice to enable meaningful prognostic comparisons and inform individualized management. Full article
(This article belongs to the Section Clinico-Pathological Correlation in Dermatopathology)
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29 pages, 45971 KB  
Article
Dual-Tracer Imaging and Deep Learning for Real-Time Prediction of Lymph Node Metastasis in cN0 Papillary Thyroid Carcinoma
by Jing Zhou, Yuchen Zhuang, Qian Xiao, Shiying Yang, Zhuolin Dai, Chun Huang, Chang Deng, Lin Chun, Han Gao and Xinliang Su
Cancers 2026, 18(7), 1157; https://doi.org/10.3390/cancers18071157 - 3 Apr 2026
Viewed by 689
Abstract
Background: Occult lymph node metastasis (LNM) occurs in 30–80% of patients with clinically node-negative papillary thyroid carcinoma (cN0-PTC), partly owing to the limited sensitivity of current preoperative nodal assessment, and may contribute to postoperative recurrence. Conventional sentinel lymph node (SLN) biopsy, typically [...] Read more.
Background: Occult lymph node metastasis (LNM) occurs in 30–80% of patients with clinically node-negative papillary thyroid carcinoma (cN0-PTC), partly owing to the limited sensitivity of current preoperative nodal assessment, and may contribute to postoperative recurrence. Conventional sentinel lymph node (SLN) biopsy, typically performed with a single tracer, has limited reliability for detecting occult metastatic nodes, which can result in either overtreatment or undertreatment with lymph node dissection. We aimed to develop a highly accurate multimodal prediction framework to accurately identify second-echelon lymph node metastasis (SeLNM) and non-sentinel lymph node metastasis (NsLNM). Methods: We prospectively enrolled 301 patients with cN0-PTC between April and October 2024, of whom 131 met the inclusion criteria. Intraoperatively, a dual-tracer technique combining carbon nanoparticles and indocyanine green was applied, and near-infrared imaging was used to record the entire SLN visualization process in real time. For each case, a 3 min video clip (150 frames) was captured. Two senior surgeons delineated regions of interest to generate 19,650 mask images. A total of 2048 spatial features and 20 temporal features were extracted, combined with 32 clinical variables, including demographics, ultrasound characteristics, and gene mutation status. Nine deep learning models were developed and evaluated using 10-fold cross-validation. Model performance was quantified using receiver operating characteristic curves, decision curve analysis curves, calibration curves, precision–recall curves, learning curves, and 12 metrics. Statistical comparisons were performed using the DeLong test, and models were further evaluated using a probability-based ranking approach. Shapley Additive Explanations (SHAP) analysis was applied to interpret key predictive features. The primary outcomes were SeLNM and NsLNM, defined based on postoperative histopathology. Results: The Long Short-Term Memory (LSTM) + Transformer model showed the best performance for both prediction tasks, with stable AUCs across training and testing (SeLNM: 0.980/0.982; NsLNM: 0.986/0.983). In the testing set, the model reached the same accuracy for both outcomes (94.7%) and showed strong sensitivity/specificity for SeLNM (94.7%/94.6%) and NsLNM (96.4%/91.5%). SHAP analysis indicated that time-series fluorescence flow features were the most influential predictors, followed by spatial structural features and SLN status. Conclusions: Dual-tracer SLN mapping with deep learning demonstrated encouraging intraoperative prediction of lymph node metastasis with interpretable features in this single-center cohort. Independent multicenter validation and prospective outcome studies are needed before considering clinical adoption. Full article
(This article belongs to the Section Cancer Informatics and Big Data)
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16 pages, 3039 KB  
Article
A Preclinical Study of a PSMA Ligand-Based Dual-Modality Probe for Radical Prostatectomy
by Haoxi Zhou, Zhiqiang Chen, Long Yi, Baojun Wang, Shaoxi Niu, Yu Gao and Xu Zhang
Pharmaceuticals 2026, 19(4), 564; https://doi.org/10.3390/ph19040564 - 1 Apr 2026
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Abstract
Purpose: Prostate-specific membrane antigen (PSMA) is a well-established molecular target in prostate cancer (PCa). Both radionuclide imaging and near-infrared fluorescence (NIRF) imaging offer high sensitivity for in vivo tumor detection. PSMA-targeted dual-modality probes integrating these two imaging techniques provide complementary preoperative and [...] Read more.
Purpose: Prostate-specific membrane antigen (PSMA) is a well-established molecular target in prostate cancer (PCa). Both radionuclide imaging and near-infrared fluorescence (NIRF) imaging offer high sensitivity for in vivo tumor detection. PSMA-targeted dual-modality probes integrating these two imaging techniques provide complementary preoperative and intraoperative tumor visualization, thereby improving surgical guidance in PCa. In this study, we aimed to develop a novel dual-labeled PSMA probe combining radioactive and fluorescent properties to achieve precise tumor delineation during radical prostatectomy (RP). Methods: A high-affinity PSMA-targeted fluorescent probe (PSMA-DF) was synthesized using solid-phase synthesis. Subsequent radiolabeling with the radionuclide [68Ga]Ga yielded the successful generation of a dual-modal PSMA-targeted molecular probe, namely [68Ga]Ga-PSMA-DF. The probe was systematically evaluated both in vitro and in vivo, and its safety profile was assessed through acute toxicity testing. Tumor-bearing nude mouse models were established using PSMA-positive 22Rv1 and PSMA-negative PC-3 PCa cell lines. Imaging performance, tumor-targeting specificity, and biodistribution of the probe were comprehensively evaluated using micro-PET imaging, in vivo fluorescence imaging, and biodistribution studies. Results: High-quality and high-purity PSMA-DF was successfully prepared, which exhibited excellent optical properties. Following radiolabeling with [68Ga]Ga, a dual-modality radionuclide-fluorescence probe ([68Ga]Ga-PSMA-DF) was successfully constructed. In vitro cellular uptake studies demonstrated that 22Rv1 cells had relatively high uptake of the probe, reaching 7.34 ± 0.55 IA%/106 cells at 120 min. In contrast, PC-3 cells and blocked 22Rv1 cells displayed minimal uptake, confirming the specific targeting ability of the probe. In vivo evaluations were conducted on tumor-bearing mice using micro-PET/CT and NIRF imaging. The results revealed that [68Ga]Ga-PSMA-DF achieved high specific tumor accumulation in 22Rv1 xenografts, with the peak tumor uptake (SUVmax = 1.748 ± 0.132) and tumor-to-muscle ratio (11.542 ± 1.511) observed at 120 min. Notably, high-contrast fluorescence imaging was also achieved at later time points, yielding a tumor-to-background ratio (TBR) of 6.559 ± 1.415 at 48 h. Notably, ex vivo biodistribution data were consistent with in vivo imaging findings. Conclusions: This preclinical study demonstrates that [68Ga]Ga-PSMA-DF exhibits high and specific uptake in PCa models, supporting its potential as a dual-modality tracer for both PET/CT imaging and real-time intraoperative fluorescence guidance during PCa surgery. Full article
(This article belongs to the Section Medicinal Chemistry)
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21 pages, 1784 KB  
Article
Evaluating the Use and Feasibility of Indocyanine Green (ICG) as a Beacon of Precision in Sentinel Node Biopsy for Breast Cancer from an Oncoplastic Practice in India
by Chaitanyanand B. Koppiker, Rupa Mishra, Vaibhav Jain, Sneha Bhandari, Namrata Athavale, Nutan Jumle, Chetan Deshmukh, Beenu Varghese, Upendra Dhar, Anushree Vartak, Pallavi Daphale, Laleh Busheri, Vishesha Lulla and Sneha Joshi
Cancers 2026, 18(6), 1042; https://doi.org/10.3390/cancers18061042 - 23 Mar 2026
Viewed by 722
Abstract
Background: Accurate axillary staging is vital in breast cancer. While dual tracers (Tc-99m + methylene blue dye) are standard for sentinel lymph node biopsy (SLNB), indocyanine green (ICG) offers a cost-effective, safe alternative, especially where nuclear medicine access is limited. Despite growing global [...] Read more.
Background: Accurate axillary staging is vital in breast cancer. While dual tracers (Tc-99m + methylene blue dye) are standard for sentinel lymph node biopsy (SLNB), indocyanine green (ICG) offers a cost-effective, safe alternative, especially where nuclear medicine access is limited. Despite growing global use, data from low- and middle-income countries (LMICs) remain scarce. This study presents India’s largest cohort using ICG in SLNB. Methods: We analyzed data from 678 breast cancer patients (2013–2023), of whom 609 underwent SLNB. For analysis, patients were grouped into: isotope + blue dye (control), ICG + blue dye (study group), and ICG alone. False-negative rate (FNR) was evaluated in cases where SLNB was followed by axillary lymph node dissection (ALND). All other outcomes were assessed across the SLNB cohort. Results: In upfront surgery, the study group had an identification rate (IR) of 95.6%, an FNR of 5%, and a median node yield of four, compared to the control group (IR 94.1%, FNR 0%, median of three). Post-neoadjuvant systemic therapy (NAST), the study group outperformed the control (IR 92% vs. 88.2%; both FNR 10%), with higher node yield (three vs. two). From 2021, ICG alone showed 100% IR, 0% FNR (upfront), and 95.6% IR (post-NACT), with high median node retrieval. Overall recurrence was 7.8%; loco-regional recurrence was 3.09%. Conclusions: ICG offers high efficacy, safety, and feasibility as a sole tracer, especially in LMICs. Its integration into SLNB and oncoplastic workflows supports its broader adoption as a practical alternative to radioisotopes in breast cancer surgery. Full article
(This article belongs to the Special Issue Recent Advances and Challenges in Breast Cancer Surgery: 2nd Edition)
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14 pages, 1194 KB  
Article
Comparative Evaluation of Sentinel Lymph Node Detection Rates in Breast Cancer Surgery: “ICG + Patent Blue” Versus “99mTc + Patent Blue”, a 11-Year Single-Center Study
by Ines Hfaiedh, Arrigo Fruscalzo, Joy Shannon Sudan, Anis Feki and Benedetta Guani
Cancers 2026, 18(6), 959; https://doi.org/10.3390/cancers18060959 - 16 Mar 2026
Viewed by 622
Abstract
Background: Breast cancer is the most common malignancy in women, and sentinel lymph node (SLN) biopsy is essential for accurate nodal staging while avoiding unnecessary axillary dissection. Aim: This study aimed to compare SLN detection rates between two dual-tracer techniques: indocyanine [...] Read more.
Background: Breast cancer is the most common malignancy in women, and sentinel lymph node (SLN) biopsy is essential for accurate nodal staging while avoiding unnecessary axillary dissection. Aim: This study aimed to compare SLN detection rates between two dual-tracer techniques: indocyanine green plus patent blue (ICG + PB) and technetium-99m plus patent blue (99mTc + PB), and to identify factors associated with detection failure for each tracer. Methods: All clinically node-negative breast cancer patients undergoing SLN biopsy between January 2014 and December 2024 were retrospectively evaluated. SLN detection was considered successful when at least one node was identified intraoperatively and confirmed histologically. Multivariate analysis assessed clinical and tumor-related predictors of failure. Results: A total of 269 procedures (258 patients) were analyzed, including 152 ICG + PB and 117 99mTc + PB procedures. Detection rates were comparable between groups (95.4% vs. 94.9%, p = 0.96), with no significant differences in the number of SLNs retrieved or nodal positivity. Multivariate analysis identified increasing patient age as the only independent predictor of PB failure, while no variables were associated with ICG failure. Tumor location in the upper-inner quadrant was the sole predictor of 99mTc failure. Conclusions: ICG + PB and 99mTc + PB provide equivalent and high SLN detection rates. ICG appears to be a robust, radiation-free alternative with no identifiable predictors of failure, supporting its role as an effective mapping strategy, particularly in centers aiming to optimize workflow and patient safety, despite the limited available data on its efficacy. Full article
(This article belongs to the Section Methods and Technologies Development)
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