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Keywords = technetium-99m (99mTc)

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25 pages, 13806 KB  
Article
Experimental and Computational Evaluation of Hybrid Bi2O3/WO3 Nanoparticle-Filled Epoxy Composites for Lead-Free Tc-99m Gamma-Ray Shielding in Occupational Radiation Protection
by Suphalak Khamruang Marshall, Phuchisa Tepnarin, Wuttipat Wattanaphonpinich and Waritthon Atsawasetthini
Polymers 2026, 18(15), 1804; https://doi.org/10.3390/polym18151804 (registering DOI) - 23 Jul 2026
Abstract
Lead-free polymer composites containing high-atomic-number fillers are promising alternatives to conventional lead shielding for nuclear medicine applications. In this study, Bi2O3-, WO3-, and hybrid Bi2O3/WO3 nanoparticle-filled epoxy resin composites were fabricated and [...] Read more.
Lead-free polymer composites containing high-atomic-number fillers are promising alternatives to conventional lead shielding for nuclear medicine applications. In this study, Bi2O3-, WO3-, and hybrid Bi2O3/WO3 nanoparticle-filled epoxy resin composites were fabricated and evaluated for attenuation of the 140 keV photons emitted by technetium-99m (Tc-99m). The synthesized Bi2O3 and WO3 nanoparticles exhibited hydrodynamic diameters of 638.2 ± 11.3 and 404.2 ± 3.2 nm, respectively, with polydispersity indices below 0.30 and zeta potentials of −33.73 ± 0.63 and −32.47 ± 0.75 mV, indicating acceptable dispersion characteristics and colloidal stability. SEM–EDX confirmed successful incorporation of Bi- and W-containing phases into the epoxy matrix, while the XRD and FTIR analyses verified retention of the crystalline metal oxide phases and the principal chemical structure of the cured epoxy network. Tensile testing revealed a composition-dependent strength–ductility relationship, with the Bi2O3-filled composite exhibiting the highest tensile strength among the developed formulations and the hybrid composite showing the greatest elongation at break. XCOM and Phy-X/PSD simulations demonstrated that increasing high-Z filler content enhanced the mass and linear attenuation coefficients and reduced the half-value layer, tenth-value layer, and mean free path. Experimental shielding performance was evaluated using Hp(10) measurements with optically stimulated luminescence dosimeters positioned on an anthropomorphic thorax phantom under a fixed Tc-99m exposure geometry. The transmitted dose decreased with increasing filler loading, and nanoparticle-filled formulations generally outperformed the corresponding conventional-particle composites. The hybrid 75:25 Bi2O3/WO3 NP composite exhibited the lowest mean Hp(10) value of 0.016 µSv, corresponding to a 50% reduction relative to the lead reference under the investigated geometry. The combined structural, mechanical, computational, and dosimetric results demonstrate that hybrid filler design enables simultaneous optimization of attenuation efficiency and mechanical tolerance. These findings identify the Bi-rich hybrid epoxy composite as a promising lead-free material for customized shielding components, including vial holders, syringe-shield housings, protective panels, and workstation accessories used during Tc-99m handling in nuclear medicine. Full article
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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 413
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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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 401
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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15 pages, 5728 KB  
Article
Clinical Value of Technetium Tc 99m Monomer Methoxy Isobutyl Isonitrile Scintigraphy for the Level of Lower-Limb Amputation in Patients with Diabetic Foot Ulcers
by Mehmet Ekici, Ali Eray Günay, Seyhan Karaçavuş, Hümeyra Gençer and Fırat Ozan
J. Am. Podiatr. Med. Assoc. 2026, 116(3), 34; https://doi.org/10.3390/japma116030034 - 21 May 2026
Viewed by 693
Abstract
Background: There is a positive relationship between mitochondrial damage in the cell and uptake in technetium Tc 99m monomer methoxy isobutyl isonitrile (99mTc-MIBI) scintigraphy. Severe mitochondrial dysfunction with cell death occurs in patients with diabetic foot ulcers (DFUs). To decide [...] Read more.
Background: There is a positive relationship between mitochondrial damage in the cell and uptake in technetium Tc 99m monomer methoxy isobutyl isonitrile (99mTc-MIBI) scintigraphy. Severe mitochondrial dysfunction with cell death occurs in patients with diabetic foot ulcers (DFUs). To decide on the level of amputation, 99mTc-MIBI scintigraphy should be considered. Methods: Prospectively, 24 patients with DFUs were included in the study. Based on treatment that started with the hospitalization, patients were divided into two groups: those whose DFUs healed and did not need surgical intervention (healed group) and those whose DFUs did not regress despite surgical and medical treatment and who required further surgical intervention (reoperation group). Before surgery, 99mTc-MIBI scintigraphy was performed. The 99mTc-MIBI uptake rates of the injured foot relative to the healthy foot were recorded. Deep-tissue culture was taken at surgery. Erythrocyte sedimentation rate, white blood cell count, and C-reactive protein (CRP) and albumin levels were measured. Results: The 99mTc-MIBI uptake rates of patients with poor prognosis were higher at all times than those of patients who did not require revision surgery. A significant difference was found between these values in the 10 and 30 s rates. The mean ± SD CRP level was 86.04 ± 21.87 mg/dL in the healed group and 144.43 ± 27.54 mg/dL in the reoperation group (p = 0.040). There was a positive correlation between ulcerated foot and healthy foot 99mTc-MIBI involvement rates at 10 and 30 s and CRP values, and a negative correlation between albumin values. Conclusions: There was a significant relationship between 99mTc-MIBI involvement rates and poor prognosis and reamputation. The correlation between CRP and albumin levels, which are among the predictive values, and 99mTc-MIBI uptake confirmed this relationship in DFUs, which are difficult to manage and treat. Full article
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19 pages, 1933 KB  
Article
Development and Evaluation of “a PEGylated Anti-Tau ScFv for SPECT Imaging” in a Rat Model of Traumatic Brain Injury
by Esmat Sajjadi, Ehsan Sharif-Paghaleh, Mohammad Akrami, Koorosh Shahpasand, Ismaeil Haririan and Samane Maghsoudian
Pharmaceutics 2026, 18(5), 626; https://doi.org/10.3390/pharmaceutics18050626 - 20 May 2026
Viewed by 714
Abstract
Background: Traumatic brain injury (TBI) affects millions of individuals annually and remains a major global cause of neurological disability and death. Tau protein hyperphosphorylation, particularly in its cis conformation, is a major pathological hallmark contributing to neurodegeneration following TBI. Single-chain variable fragments (scFvs), [...] Read more.
Background: Traumatic brain injury (TBI) affects millions of individuals annually and remains a major global cause of neurological disability and death. Tau protein hyperphosphorylation, particularly in its cis conformation, is a major pathological hallmark contributing to neurodegeneration following TBI. Single-chain variable fragments (scFvs), despite their diagnostic potential, suffer from rapid renal clearance and short circulation half-lives, which limit their in vivo performance. PEGylation is therefore employed to prolong systemic circulation and improve the pharmacokinetic behavior of scFvs, enabling more effective brain retention and target engagement. Methods: In this study, we utilized a previously validated anti-cis p-tau scFv antibody fragment, radiolabeled with technetium-99m tricarbonyl (99mTc(CO)3), as a diagnostic tracer to detect tau pathology in TBI rat models. The antibody was conjugated with polyethylene glycol (PEG, 20 kDa); PEGylation efficiency was determined by quantifying the products on SDS-PAGE, and the products were subsequently radiolabeled. Results: Radiochemical purity (RCP) was ~95.4% for the non-PEGylated tracer (99mTc-AININ20) and ~92.7% for the PEGylated form (99mTc-AININ20-PEG), with both showing >90% radiochemical purity consistently. Upon systemic administration, PEGylated scFv was able to cross the blood–brain barrier (BBB) and selectively accumulated in injured regions, as confirmed by single-photon emission computed tomography (SPECT) imaging. Both PEGylated and non-PEGylated scFv tracers showed significantly higher brain uptake in TBI rats compared to healthy controls (p < 0.0001). At 24 h, the PEGylated form exhibited a significantly higher brain signal than the non-PEGylated version (p < 0.0001), indicating improved tracer retention. Biodistribution analysis at 2 h post-injection showed significantly reduced renal clearance for the PEGylated tracer and increased hepatic uptake compared to the non-PEGylated form. At 24 h, in vivo imaging confirmed sustained brain retention, highlighting improved pharmacokinetics and imaging potential. Conclusions: These results support PEGylated scFv as a promising SPECT imaging agent for early detection of tauopathy in TBI, offering enhanced brain retention and improved pharmacokinetics. Full article
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14 pages, 597 KB  
Article
Tc-99m DMSA Radiomics in CKD: Phenotype-Specific Cortical Signatures and a Morphological Predictor of Renal Function Decline
by Mustafa Demir, Nihat Köylüce, Davut Eren, Koray Uludağ, Hümeyra Gençer, Seyhan Karaçavuş and Fadime Demir
Diagnostics 2026, 16(9), 1351; https://doi.org/10.3390/diagnostics16091351 - 30 Apr 2026
Viewed by 426
Abstract
Purpose: This study aims to evaluate the ability of radiomic features obtained from technetium-99m dimercaptosuccinic acid (Tc-99m DMSA) planar images to distinguish renal cortical uptake patterns among patients with chronic kidney disease (CKD). We also assessed the association between selected radiomic features [...] Read more.
Purpose: This study aims to evaluate the ability of radiomic features obtained from technetium-99m dimercaptosuccinic acid (Tc-99m DMSA) planar images to distinguish renal cortical uptake patterns among patients with chronic kidney disease (CKD). We also assessed the association between selected radiomic features and progressive renal function loss during follow-up. Methods: The study included a total of 185 patients: patients with Diabetes mellitus (DM) + hypertension (HTN) diagnosis (Group 1, n = 30), patients with HTN diagnosis alone (Group 2, n = 86), and patients with no history of DM or HTN who were followed for CKD (Group 3, n = 69). Intergroup comparisons were performed using the Kruskal–Wallis test with Bonferroni-corrected post hoc pairwise testing; the proportion of significantly different features was assessed using FDR correction. As a secondary exploratory analysis, the relationship between selected radiomic features and time to first observed ≥20% eGFR decline at follow-up was evaluated using univariate L2-penalised Cox proportional hazards regression with feature selection guided by the events-per-variable principle and model discrimination quantified using Harrell’s C-index. Results: Intensity Kurtosis values showed a statistically significant difference among the groups: −0.11 (−0.31 to 0.12) for Group 1, −0.24 (−0.41 to −0.04) for Group 2, and −0.33 (−0.45 to −0.16) for Group 3 (p = 0.001). Mean Intensity values were found to be 60.66 (31.01–89.39) in Group 1 and 90.46 (72.87–106.34) in Group 3 (p < 0.001). Age, gender, and baseline eGFR did not differ between groups. Radiomic analysis revealed significant intergroup differences predominantly in intensity- and texture-based features, while morphological features showed more limited differentiation. In the secondary exploratory longitudinal analysis, Centre of Mass Shift was the only morphological feature significantly associated with time to first observed ≥20% eGFR decline at follow-up (HR per SD: 0.74; 95% CI: 0.58–0.94; p = 0.015; C-index: 0.57). Conclusions: Radiomic features from Tc-99m DMSA planar images reveal quantitative differences between clinically defined CKD subgroups even when cortical uptake appears visually indistinguishable. The threshold-specific association of Centre of Mass Shift with subsequent eGFR decline, beyond baseline renal function, suggests that DMSA radiomics may provide exploratory prognostic information that warrants prospective validation. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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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 707
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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13 pages, 5109 KB  
Article
Biodistribution of Tc-99m-Labeled Solid Lipid Nanoparticles and Evaluation of Their Possibility as a Radiopharmaceutical
by Hayrettin Eroglu, Arif Kürsad Ayan and Ayse Yenilmez
Molecules 2026, 31(4), 654; https://doi.org/10.3390/molecules31040654 - 13 Feb 2026
Cited by 3 | Viewed by 716 | Correction
Abstract
Solid lipid nanoparticles (SLNs) are submicron colloidal systems widely investigated as drug carriers; however, their intrinsic biodistribution properties are also critical when SLNs are considered for diagnostic imaging. In the present proof-of-concept study, drug-free SLNs were evaluated exclusively as a radiolabeled imaging agent [...] Read more.
Solid lipid nanoparticles (SLNs) are submicron colloidal systems widely investigated as drug carriers; however, their intrinsic biodistribution properties are also critical when SLNs are considered for diagnostic imaging. In the present proof-of-concept study, drug-free SLNs were evaluated exclusively as a radiolabeled imaging agent rather than as a drug delivery system. SLNs were radiolabeled with Technetium-99m (99mTc), and their in vivo biodistribution was investigated using gamma camera imaging, ex vivo organ counting, and confocal microscopy. SLNs were prepared by a microemulsion–low-temperature solidification method and characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). Radiolabeling efficiency was determined by instant thin-layer chromatography (ITLC) and exceeded 95%. Following intravenous administration in a rabbit model, dynamic scintigraphic imaging demonstrated predominant uptake in the liver and spleen. These findings were quantitatively confirmed by ex vivo biodistribution analysis at 4 h post-injection and qualitatively supported by confocal microscopy of liver and spleen tissues. The results indicate that 99mTc-labeled SLNs behave as RES-targeting radiocolloids and may serve as potential agents for liver–spleen scintigraphy. Full article
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20 pages, 3611 KB  
Article
From [99mTc]pertechnetate to [99mTc]sestamibi: Dissection of a Complex Reaction Sequence Using Radio-LC-MS
by Joana do Mar Ferreira Machado, Antonio Shegani, Ingebjørg N. Hungnes, Truc T. Pham, Amaia Carrascal-Miniño, Margaret S. Cooper, Victoria Gibson, Levente K. Meszaros, Michelle T. Ma and Philip J. Blower
Molecules 2026, 31(4), 596; https://doi.org/10.3390/molecules31040596 - 9 Feb 2026
Viewed by 892
Abstract
[99mTc]sestamibi ([99mTc][Tc(MIBI)6]+; MIBI = 2-methoxybutylisonitrile) is a clinically established myocardial perfusion SPECT tracer. Its one-pot kit-based synthesis from [99mTc]pertechnetate ([99mTc][TcO4]) is complex, involving a 6-oxidation state transition [...] Read more.
[99mTc]sestamibi ([99mTc][Tc(MIBI)6]+; MIBI = 2-methoxybutylisonitrile) is a clinically established myocardial perfusion SPECT tracer. Its one-pot kit-based synthesis from [99mTc]pertechnetate ([99mTc][TcO4]) is complex, involving a 6-oxidation state transition (Tc(VII) to Tc(I)) and complete ligand replacement. We aimed to unravel this complex reaction, to inform rational quality control and identify new technetium synthons for molecular imaging. Generator-produced [99mTc]pertechnetate was added to commercial or bespoke clinically used kits, varying the reaction time, temperature, and concentrations of reagents (individually and collectively) and carrier technetium-99. Radioactive products were analysed by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) with optical, radiometric, and mass spectrometric (MS-ESI+) detection. At least 11 radioactive intermediates were detected by radio-HPLC. Technetium(V) and technetium(I) intermediates were identified or imputed by radio-HPLC-MS, including [TcVO(cysteinate)2]+, [TcI(MIBI)4L2]+, and [TcI(MIBI)5L1]+ (L = labile monodentate ligand, e.g., H2O). Tc(III) intermediates [TcIII(cysteinate)2(MIBI)]+ and [TcIII(cysteinate)2(MIBI)2]+ were indicated by weak MS-ESI+ ions. We conclude that the reaction proceeds via reduction from [TcVIIO4] via unknown intermediates to [TcVO(cysteinate)2]+, then via Tc(III) intermediates containing both cysteinate and MIBI ligands (e.g., [TcIII(cysteinate)2(MIBI)2]+), to form Tc(I) without cysteine and with <6 MIBI ligands, followed by further ligand displacement by MIBI to form [Tc(MIBI)6]+. Once formed, [Tc(MIBI)6]+ undergoes no further reaction. Full article
(This article belongs to the Special Issue New Advances in Radiopharmaceutical Sciences, 2nd Edition)
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14 pages, 3732 KB  
Systematic Review
Indocyanine Green (ICG) Fluorescence vs. Tc-99m Lymphoscintigraphy: Optimizing Sentinel Lymph Node Detection in Cutaneous Melanoma—A Systematic Review and Meta-Analysis
by Matteo Matteucci, Antonio Pesce, Bruno Cirillo, Lorenza Zampino, Riccardo Masserano, Salvatore Guarino, Luca Properzi, Vito D’Andrea and Roberto Cirocchi
J. Clin. Med. 2026, 15(3), 1145; https://doi.org/10.3390/jcm15031145 - 2 Feb 2026
Viewed by 747
Abstract
Background: Sentinel lymph node (SLN) biopsy has emerged as a cornerstone in melanoma staging, offering targeted evaluation of regional lymphatic spread and guiding therapeutic decision-making. Traditionally, SLN mapping relies on lymphoscintigraphy using technetium-99m (Tc-99m) radiocolloid, but in recent years, indocyanine green (ICG) [...] Read more.
Background: Sentinel lymph node (SLN) biopsy has emerged as a cornerstone in melanoma staging, offering targeted evaluation of regional lymphatic spread and guiding therapeutic decision-making. Traditionally, SLN mapping relies on lymphoscintigraphy using technetium-99m (Tc-99m) radiocolloid, but in recent years, indocyanine green (ICG) fluorescence imaging has emerged as a promising alternative. The aim of this review is to evaluate the diagnostic accuracy of ICG–near-infrared (NIR) imaging compared to standard Tc-99m lymphoscintigraphy in SLN biopsy (SLNB). Methods: A systematic review and meta-analysis were conducted, including 12 studies. The primary outcome was the false-negative rate; secondary outcomes included the total number of sentinel lymph nodes (SLNs) identified by ICG–NIR imaging and Tc-99m lymphoscintigraphy, the number of metastatic SLNs detected by each method, and the number of patients with metastatic disease. The statistical analysis for dichotomous variables was performed using the “Odds Ratio” (O.R.) calculated with the Mantel–Haenszel method. For continuous variables, the analysis utilized the “Mean Difference” calculated by the inverse variance method. All data are presented with a 95% confidence interval (CI). Results: ICG was associated with a significantly higher number of SLNs identified compared to Tc-99m (O.R.: 0.41, 95% CI: 0.34–0.49; p < 0.00001), while no significant differences were found in the detection of metastatic nodes, either as a proportion of total SLNs (O.R.: 1.04, 95% CI: 0.86–1.25; p = 0.68) or relative to total positive nodes (O.R.: 0.36, 95% CI: 0.16–0.81; p = 0.01). No statistically significant differences between the two techniques were found in the detection of metastatic patients (OR: 0.80, 95% CI: 0.31–2.03, p = 0.33) and in the total number of false-negative patients missed (risk difference (RD): 0.03, 95% CI: −0.04 to 0.09, p = 0.93). Conclusions: While ICG identifies a higher number of SLNs compared to Tc-99m, its ability to detect metastatic involvement is comparable between the two modalities. No significant differences were observed in the proportion of metastatic SLNs, the total number of positive nodes detected, the number of metastatic patients identified, and the false-negative rate. Given its favorable profile, ICG could represent a reliable alternative or adjunct to Tc-99 in SLNB. However, prospective studies are warranted to validate its standalone diagnostic role. Full article
(This article belongs to the Special Issue Clinical Advances in the Management of Melanoma)
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15 pages, 2675 KB  
Review
Incidental Cardiac Uptake on 99mTc-HMDP Bone Scintigraphy in Oncology Patients: Two Cases of Transthyretin Amyloid Cardiomyopathy with Literature Review
by Naoya Matsuki, Toru Awaya, Jin Endo, Taeko Kunimasa, Tatsuya Gomi, Yasushi Okamoto and Hidehiko Hara
Diseases 2026, 14(1), 23; https://doi.org/10.3390/diseases14010023 - 7 Jan 2026
Viewed by 1512
Abstract
Background: Bone scintigraphy using technetium-99m hydroxymethylene diphosphonate (99mTc-HMDP) is extensively employed to detect bone metastases. However, incidental myocardial uptake may indicate wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM), a frequently overlooked diagnosis with important clinical implications. Case Presentation: Two elderly female patients with [...] Read more.
Background: Bone scintigraphy using technetium-99m hydroxymethylene diphosphonate (99mTc-HMDP) is extensively employed to detect bone metastases. However, incidental myocardial uptake may indicate wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM), a frequently overlooked diagnosis with important clinical implications. Case Presentation: Two elderly female patients with a history of breast cancer were subjected to 99mTc-HMDP bone scintigraphy as part of a routine evaluation for possible bone metastases. Both cases demonstrated incidental myocardial uptake (Perugini Grade 2 and Grade 3, respectively), raising suspicion for ATTRwt-CM, which was subsequently confirmed by endomyocardial biopsy. Review of the Literature: We reviewed published studies reporting cardiac uptake on bone scintigraphy, summarizing the frequency, patient demographics, and tracer types, and emphasizing the clinical relevance of this finding in cancer patients. Conclusions: In oncology patients, bone scintigraphy performed during routine metastatic screening may facilitate early detection of ATTRwt-CM, enabling timely diagnosis and treatment initiation, potentially improving clinical outcomes. Full article
(This article belongs to the Special Issue Feature Papers in Section 'Cardiology' in 2024–2025)
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26 pages, 3274 KB  
Review
Cyclopentadienyl Complexes of Technetium
by Ulrich Abram and Maximilian Roca Jungfer
Molecules 2025, 30(24), 4813; https://doi.org/10.3390/molecules30244813 - 18 Dec 2025
Cited by 3 | Viewed by 1158
Abstract
The number of structurally investigated cyclopentadienyl (Cp) complexes of technetium is limited in contrast to the situation with its heavier homolog, rhenium. Although this could be attributed to the radioactivity of all isotopes of the radioelement, there are also clear chemical [...] Read more.
The number of structurally investigated cyclopentadienyl (Cp) complexes of technetium is limited in contrast to the situation with its heavier homolog, rhenium. Although this could be attributed to the radioactivity of all isotopes of the radioelement, there are also clear chemical differences to analogous compounds of the other group seven elements, manganese and rhenium. Technetium Cp compounds are known with the metal in the oxidation states “+1” to “+7”, with a clear dominance of Tc(I) carbonyls and nitrosyls. Corresponding carbonyl complexes also play a significant role in the development of 99mTc-based radiopharmaceuticals with the aromatic ring as an ideal position for the attachment of biomarkers. In this paper, the present status of the synthetic and structural chemistry of technetium with Cp ligands is discussed, together with recent developments in the corresponding 99mTc labeling chemistry. Full article
(This article belongs to the Special Issue Advances in Metallocene Chemistry)
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11 pages, 1534 KB  
Article
Triple-Tracer Sentinel Node Mapping: Maximizing Detection, Minimizing Dissection
by Daniel Alin Cristian, Bogdan Popescu, Cristian Valentin Toma, Sertaç Ata Güler, Adrian Bordea, Emil Popa, Draga-Maria Mandi, Bianca Maria Floarea and Răzvan-Valentin Scăunaşu
Life 2025, 15(12), 1839; https://doi.org/10.3390/life15121839 - 29 Nov 2025
Viewed by 730
Abstract
Background: Sentinel lymph node (SLN) biopsy often combines technetium-99m (99mTc), indocyanine green (ICG), and methylene blue (MB), but few contemporary audits quantify the performance of each tracer when used together in routine practice. Methods: We conducted a single-center retrospective audit of 111 consecutive [...] Read more.
Background: Sentinel lymph node (SLN) biopsy often combines technetium-99m (99mTc), indocyanine green (ICG), and methylene blue (MB), but few contemporary audits quantify the performance of each tracer when used together in routine practice. Methods: We conducted a single-center retrospective audit of 111 consecutive SLN procedures for breast cancer patients undergoing SLNB using a triple-tracer approach with technetium-99m (99mTc), indocyanine green (ICG), and methylene blue (MB). We evaluated sentinel lymph node detection rates, the number of nodes retrieved, tracer concordance, and subgroup performance (including those with mastectomy and post-neoadjuvant therapy). Results: Identification was 96.4% for 99mTc (107/111), 93.7% for ICG (104/111), and 78.4% for MB (87/111). Performance was heterogeneous (Q = 26.2, p < 0.001); 99mTc and ICG each outperformed MB (Holm-adjusted p < 0.001), while 99mTc and ICG did not differ significantly. Triple-tracer workflows were associated with higher odds of detection; cross-validated AUCs reached 0.98 for 99mTc and 0.82 for ICG. Conclusions: Technetium remains a foundational tracer for SLNB, with ICG serving as a valuable adjunct that enhances nodal visualization and overall detection efficacy, and MB adds redundancy. Triple-tracer mapping achieved the best overall nodal identification and was associated with fewer sentinel nodes excised when complete tracer concordance was observed. Full article
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20 pages, 1754 KB  
Article
Synthesis and Biological Evaluation of Novel Mixed-Ligand 99mTc-Labeled Anthraquinone Complexes as Potential DNA-Targeted Imaging Agents
by Theofanis Matthaios Migkos, Pigi Glykofridi, Georgios Paparidis, George Psomas, Ioannis S. Vizirianakis, Catherine Gabriel, Dimosthenis Sarigiannis, Ioannis Iakovou and Dionysia Papagiannopoulou
Inorganics 2025, 13(11), 368; https://doi.org/10.3390/inorganics13110368 - 3 Nov 2025
Cited by 1 | Viewed by 1212
Abstract
Anthraquinones are molecules with numerous biological properties that can act as DNA intercalators and topoisomerase IIa inhibitors. In this work, the development of technetium-99m radiotracers was pursued via the technetium-tricarbonyl “2 + 1” mixed-ligand approach, fac-[99mTc][TcI(CO)3(NN′)(N)] [...] Read more.
Anthraquinones are molecules with numerous biological properties that can act as DNA intercalators and topoisomerase IIa inhibitors. In this work, the development of technetium-99m radiotracers was pursued via the technetium-tricarbonyl “2 + 1” mixed-ligand approach, fac-[99mTc][TcI(CO)3(NN′)(N)]+, with a (N,N′) bidentate chelator and a N co-ligand. In one approach, the ligands used were 2,2′-bipyridine (bpy) and N-functionalized-imidazole, where imidazole was conjugated to an anthraquinone moiety. In the other approach, 2-picolylamine and imidazole were used as the mixed-ligand system, where picolylamine was conjugated to an anthraquinone moiety. The synthesis of the ligands was achieved by reaction of 2-picolylamine with a suitably functionalized anthraquinone (Aqpa) or anthrapyrazole (Appa) and imidazole with a suitably functionalized anthraquinone (Aqim). The rhenium reference compounds, fac-[ReI(CO)3(bpy)(Aqim)]+ with bpy as a bidentate chelator and fac-[ReI(CO)3(Aqpa or Appa)(Im)]+, with imidazole (Im) as a co-ligand, were synthesized and characterized with spectroscopic methods. The radiotracer technetium-99m complexes fac-[99mTc][Tc(CO)3(bpy)(Aqim)]+ and fac-[99mTc][Tc(CO)3(Aqpa or Appa)(Im)]+ were prepared and characterized with standard methods. The purified radiotracers displayed high stability (≥90%) after incubation 24 h in 1 mM L-histidine or rat plasma. The tracers’ cell uptake was evaluated in vitro in CT-26 cells, and their pharmacokinetic properties and tumor uptake were evaluated in vivo in CT26-tumor-bearing mice. The “2 + 1” technetium-tricarbonyl approach leads to in vitro stable tracers, and this mixed-ligand system shows promise for further evaluation. Full article
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14 pages, 937 KB  
Article
From Gamma Rays to Green Light: Comparative Efficacy of Indocyanine Green and Technetium-99m in Sentinel Lymph Node Biopsy for Breast Cancer
by Vlad Alexandru Gâta, Radu Alexandru Ilieș, Nicoleta Zenovia Antone, Roxana Pintican, Codruț Cosmin Nistor-Ciurba, Ștefan Țîțu, Alex Victor Orădan, Maximilian Vlad Muntean, Gheorghe Gerald Filip, Alexandru Irimie and Patriciu Andrei Achimaș-Cadariu
Med. Sci. 2025, 13(4), 231; https://doi.org/10.3390/medsci13040231 - 13 Oct 2025
Cited by 2 | Viewed by 1496
Abstract
Background/Objectives: Sentinel lymph node biopsy (SLNB) is currently the standard approach for axillary staging in breast cancer. Conventional techniques are radioisotope-based (Technetium-99m, Tc99m) and remain widely used, but novel tracers like Indocyanine Green (ICG) fluorescence provide potential advantages regarding feasibility and logistics. [...] Read more.
Background/Objectives: Sentinel lymph node biopsy (SLNB) is currently the standard approach for axillary staging in breast cancer. Conventional techniques are radioisotope-based (Technetium-99m, Tc99m) and remain widely used, but novel tracers like Indocyanine Green (ICG) fluorescence provide potential advantages regarding feasibility and logistics. Methods: We conducted a prospective, observational study including 476 female patients diagnosed with primary invasive breast cancer who underwent SLNB at the Institute of Oncology “Prof. Dr. I. Chiricuță”, Cluj-Napoca, Romania, between January 2022 and May 2025. Clinical, surgical, and pathological variables were systematically extracted. SLNB was performed using either Tc99m or ICG, according to institutional protocols. Comparative analyses were performed to evaluate sentinel node characteristics, histopathological parameters, and positive surgical margins predictors. Results: The median age was 60 years (IQR: 52–69). Breast-conserving surgery (BCS) was performed in 77.9% of cases, while mastectomy was performed in 22.1%. Sentinel lymph node positivity was reported in 25.6% of cases, with no significant differences in the number of excised or metastatic nodes between Tc99m and ICG (mean nodes: 3.23 vs. 3.20, p = 0.860; mean positive nodes: 0.35 vs. 0.36, p = 0.897). Histologically, invasive carcinoma NST was predominant (90.1%), and surgical margins were negative in 96.8% of patients, with all margin-positive cases occurring following BCS. No pathological markers (grade, Ki67, TILs, DCIS extent) predicted margin status or nodal involvement. Notably, younger age correlated inversely with the extent of ductal carcinoma in situ (r = −0.21, p < 0.00001). Conclusions: Tc99m and ICG provided comparable diagnostic performance in performing SLNB, with equivalent rates of nodal detection and pathological yield. These findings support that ICG is a safe and effective alternative for routine axillary staging in breast cancer. Full article
(This article belongs to the Section Cancer and Cancer-Related Research)
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