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Search Results (943)

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Keywords = 18F-FDG-PET/CT

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12 pages, 1222 KB  
Article
Impact of Deep-Learning-Based Respiratory Motion Correction on [18F] FDG PET/CT Test–Retest Reliability and Consistency of Tumor Quantification in Patients with Lung Cancer
by Shijia Weng, Limei Jiang, Runze Wu, Yuanyan Cao, Yuan Li and Qian Wang
Biomedicines 2026, 14(1), 245; https://doi.org/10.3390/biomedicines14010245 - 21 Jan 2026
Viewed by 110
Abstract
Objectives: Respiratory motion degrades the quantitative accuracy and test–retest (TRT) reliability of fluorine-18 fluorodeoxyglucose ([18F] FDG) positron emission tomography (PET)/computed tomography (CT) in lung cancer. This study investigated whether a deep-learning-based respiratory motion correction (RMC) method improves the TRT reliability and [...] Read more.
Objectives: Respiratory motion degrades the quantitative accuracy and test–retest (TRT) reliability of fluorine-18 fluorodeoxyglucose ([18F] FDG) positron emission tomography (PET)/computed tomography (CT) in lung cancer. This study investigated whether a deep-learning-based respiratory motion correction (RMC) method improves the TRT reliability and image quality of [18F] FDG PET tumor quantification compared with non-motion-corrected (NMC) reconstructions. Methods: Thirty-one patients with primary lung cancer underwent three PET acquisitions: whole body free breathing (Scan1), thoracic free breathing (Scan2), and thoracic controlled breathing (ScanCB). Each dataset was reconstructed with and without RMC. Visual assessments of liver motion artifacts, lesion clarity, and PET-CT co-registration were scored. Lung tumors were segmented to derive standardized uptake value max (SUVmax), SUVmean, metabolic tumor volume (MTV), PET-derived lesion length (PLL), and total lesion glycolysis (TLG). Visual image scores and TRT reliability of tumor quantification were compared using Kruskal–Wallis one-way analysis of variance and intraclass correlation coefficients (ICCs). Results: RMC reconstructions achieved higher visual scores of lesion clarity and PET-CT co-registration across all lung lobes and significantly reduced liver motion artifacts compared with NMC reconstructions. Differences in SUVmax, SUVmean, PLL, MTV, and TLG between Scan2 and ScanCB were significantly smaller with RMC than with NMC. ICCs for SUVmax, SUVmean, MTV, and TLG were higher between scans with RMC than NMC reconstructions, indicating improved TRT reliability. Conclusions: The deep-learning-based RMC method improved the image quality and TRT reproducibility of [18F] FDG PET/CT quantification in lung cancer, supporting its potential for routine adoption in therapy-response assessments. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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13 pages, 719 KB  
Article
Prognostic Value of 18F-FDG PET/CT-Derived Secondary Lymphoid Organ Ratios and Hematologic Inflammation Markers in Advanced Non-Small Cell Lung Cancer Treated with Nivolumab
by Erkam Kocaaslan, Ali Kaan Güren, Fırat Akagündüz, Ahmet Demirel, Mustafa Alperen Tunç, Burak Paçacı, Yeşim Ağyol, Pınar Erel, Abdüssamed Çelebi, Selver Işık, Ezgi Çoban, Nazım Can Demircan, Salih Özgüven, Zeynep Ceren Balaban Genç, Nargiz Majidova, Nadiye Sever, Murat Sarı, Osman Köstek and Ibrahim Vedat Bayoğlu
J. Clin. Med. 2026, 15(2), 798; https://doi.org/10.3390/jcm15020798 - 19 Jan 2026
Viewed by 138
Abstract
Background/Objectives: This study aimed to evaluate the prognostic value of 18F-FDG PET/CT-based secondary lymphoid organ metabolic ratios—spleen/liver (SLR), bone marrow/liver (BLR), and ileocecal region/liver (ILR)—and hematological inflammation markers (neutrophil/lymphocyte ratio [NLR] and systemic immune-inflammation index [SII]) obtained before nivolumab treatment in relation [...] Read more.
Background/Objectives: This study aimed to evaluate the prognostic value of 18F-FDG PET/CT-based secondary lymphoid organ metabolic ratios—spleen/liver (SLR), bone marrow/liver (BLR), and ileocecal region/liver (ILR)—and hematological inflammation markers (neutrophil/lymphocyte ratio [NLR] and systemic immune-inflammation index [SII]) obtained before nivolumab treatment in relation to survival in patients with advanced non-small cell lung cancer (NSCLC). Methods: This retrospective single-center study included 79 advanced NSCLC patients who were treated with nivolumab monotherapy at Marmara University Faculty of Medicine Hospital between 2022 and 2024. Pretreatment SLR, BLR, and ILR ratios were calculated from 18F-FDG PET/CT examinations; NLR and SII values were obtained from hematological data. Survival outcomes were analyzed using the Kaplan–Meier method, and prognostic factors were assessed using Cox proportional hazards regression analysis. In a subset of patients, an exploratory longitudinal analysis was performed using early follow-up PET/CT to assess follow-up-to-baseline changes in immune-organ metabolic ratios in relation to overall survival. Results: High NLR and SII levels were significantly associated with shorter progression-free survival and overall survival. In contrast, no significant associations were observed between PET/CT-derived metabolic ratios (SLR, BLR, and ILR) and survival. Multivariate analysis identified the presence of liver metastases and a high NLR as independent adverse prognostic factors for overall survival. Conclusions: In this homogeneous real-world cohort treated exclusively with single-agent nivolumab, PET/CT-derived secondary lymphoid organ metabolic ratios showed limited prognostic value at baseline and during early on-treatment assessment. In contrast, hematological inflammation markers, especially high NLR levels, are strong prognostic indicators of survival and may complement established clinical factors in risk stratification. Full article
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11 pages, 778 KB  
Article
Association Between PET/CT Metabolic Parameters and Serum ACE and Calcium Levels in Sarcoidosis
by Yaşar Incekara, Erdoğan Cetinkaya, Ramazan Eren, Reşit Akyel and Mustafa Cortuk
Diagnostics 2026, 16(2), 278; https://doi.org/10.3390/diagnostics16020278 - 15 Jan 2026
Viewed by 159
Abstract
Background: Sarcoidosis is a multisystem inflammatory disorder characterized by non-caseating granulomas, most commonly affecting the lungs and intrathoracic lymph nodes. Angiotensin-converting enzyme (ACE) levels and calcium abnormalities are recognized biomarkers, while ^18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is increasingly used to assess disease [...] Read more.
Background: Sarcoidosis is a multisystem inflammatory disorder characterized by non-caseating granulomas, most commonly affecting the lungs and intrathoracic lymph nodes. Angiotensin-converting enzyme (ACE) levels and calcium abnormalities are recognized biomarkers, while ^18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is increasingly used to assess disease activity. However, neither provides sufficient diagnostic accuracy alone. Therefore, this study aimed to investigate the relationship between FDG-PET/CT metabolic findings and serum ACE and calcium (Ca2+) levels as surrogate indicators of inflammatory metabolic intensity in sarcoidosis. Methods: In this retrospective single-center study, 127 patients with pulmonary sarcoidosis who underwent PET/CT at diagnosis were evaluated. Demographic and clinical data, ACE, and Ca2+ levels were recorded. FDG uptake in mediastinal, pulmonary, and extrapulmonary sites was analyzed, and correlations with biomarkers were assessed. Results: The cohort included 89 females (70.1%) and 38 males (29.9%), mean age 51.3 ± 11.9 years. FDG uptake was most frequent in mediastinal lymph nodes (84.3%) and lung parenchyma (40.9%). ACE levels correlated weakly with total SUVmax (r = 0.214, p = 0.019). Calcium levels correlated with extrapulmonary SUVmax (r = 0.327, p = 0.001) and were higher in patients with extrapulmonary involvement (p = 0.045). No associations were found between symptom presence and biomarkers or SUVmax values. Conclusions: FDG-PET/CT metabolic parameters, particularly total and extrapulmonary SUVmax, demonstrated modest yet statistically significant associations with ACE and calcium levels. These findings suggest that a combined biomarker-imaging approach may provide complementary information regarding inflammatory metabolic intensity and systemic involvement; however, the results should be interpreted as exploratory and require validation in prospective studies. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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11 pages, 692 KB  
Article
Unmasking Early Cardiac Fibrosis in Sarcoidosis: The Role of Plasma Aldosterone and Cardiac MRI
by Elias Giallafos, Evangelos Oikonomou, Niki Lama, Spiros Katsanos, Lykourgos Kolilekas, Evaggelos Markozanes, Varvara Pantoleon, Kostas Zisimos, Ourania Katsarou, Panagiotis Theofilis, Gesthimani Seitaridi, Ioannis Ilias, Grigoris Stratakos, Nikos Kelekis, Effrosyni D. Manali, Spiros Papiris, Georgios Marinos, Konstantinos Tsioufis and Gerasimos Siasos
J. Clin. Med. 2026, 15(2), 650; https://doi.org/10.3390/jcm15020650 - 14 Jan 2026
Viewed by 134
Abstract
Background/Objectives: Cardiac sarcoidosis (CS) is a challenging diagnosis due to its subclinical progression and the limitations of existing screening tools. Cardiac magnetic resonance (CMR) and PET/CT imaging have improved diagnosis and detection. Aldosterone, a hormone with known profibrotic effects, may offer additional diagnostic [...] Read more.
Background/Objectives: Cardiac sarcoidosis (CS) is a challenging diagnosis due to its subclinical progression and the limitations of existing screening tools. Cardiac magnetic resonance (CMR) and PET/CT imaging have improved diagnosis and detection. Aldosterone, a hormone with known profibrotic effects, may offer additional diagnostic value. We therefore aimed to determine whether plasma aldosterone level is associated with myocardial fibrosis, independent of active inflammation, in CS. Methods: This observational study included 541 patients with biopsy-proven sarcoidosis and preserved left ventricular ejection fraction (LVEF ≥ 50%). All underwent CMR with extracellular volume (ECV) mapping and 18F-FDG PET/CT to assess myocardial fibrosis and inflammation, respectively. Plasma aldosterone levels were also measured. Results: Plasma aldosterone levels were significantly higher in patients with cardiac sarcoidosis (172 [IQR 106–235] pg/mL) compared to those without cardiac involvement (143 [100–205] pg/mL, p = 0.02). Aldosterone was independently associated with the presence of late gadolinium enhancement (LGE) on CMR (OR 1.002 per 1 pg/mL increase; 95% CI 1.001–1.004, p = 0.04) and with higher ECV values (β = 0.008 per 1 pg/mL, p = 0.001). Regression analysis showed that aldosterone is associated with ECV (b-0.009, CI: 0.002–0.016, p = 0.009) and there was no interaction according to LGE status indicating a relationship with diffuse myocardial fibrosis even in the absence of visible scarring. No association was observed with T1-, T2-, or PET/CT-defined inflammation. Conclusions: Plasma aldosterone is a robust marker of myocardial fibrosis in sarcoidosis, particularly in early or subclinical stages. Its correlation with ECV—but not with inflammatory imaging markers—suggests its link with myocardial diffuse fibrotic remodeling before, and independently of, overt scarring or inflammation. Full article
(This article belongs to the Section Cardiovascular Medicine)
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19 pages, 1296 KB  
Article
68Ga-FAPI-04 PET/CT in the Diagnosis of Hepatocellular Carcinoma Associated with Cirrhosis: Diagnostic Value, Correlation Between PET Parameters of the Tumor and Its Size, and PIVKA-II Levels
by Zhamilya Zholdybay, Zhanar Zhakenova, Bekzhan Issamatov, Madina Gabdullina, Yevgeniya Filippenko, Suriya Yessentayeva, Galymzhan Alisherov, Jandos Amankulov and Ildar Fakhradiyev
Diagnostics 2026, 16(2), 249; https://doi.org/10.3390/diagnostics16020249 - 13 Jan 2026
Viewed by 253
Abstract
Background/Objectives: Hepatocellular carcinoma remains a major cause of death from cancer globally. While 18F-FDG PET/CT is commonly used for tumor imaging, its sensitivity is limited, especially due to high liver background uptake. Recently, 68Ga-FAPI PET/CT, which targets fibroblast activation protein in [...] Read more.
Background/Objectives: Hepatocellular carcinoma remains a major cause of death from cancer globally. While 18F-FDG PET/CT is commonly used for tumor imaging, its sensitivity is limited, especially due to high liver background uptake. Recently, 68Ga-FAPI PET/CT, which targets fibroblast activation protein in tumor stroma, has emerged as a promising diagnostic tool. In this study, we aimed to assess the diagnostic performance of 68Ga-FAPI-04 PET/CT in HCC patients with and without liver cirrhosis and to explore the relationship between PET metrics, tumor size, and PIVKA-II serum marker. Methods: In this prospective single-center study, 59 patients with confirmed HCC (37 with cirrhosis, 22 without) underwent 68Ga-FAPI-04 PET/CT. The standard dose (1.5–2.0 MBq/kg) was administered intravenously, and imaging was carried out 60 min post-injection. Semi-quantitative parameters including SUVmax, SUVmean, and tumor-to-background ratio were calculated. Diagnostic performance was assessed using histopathology and multimodal imaging. Statistical analyses included the Mann–Whitney U test and Spearman correlation. Results: The overall sensitivity for HCC detection was 89.8%, with a specificity of 60% and accuracy of 87%. Sensitivity and specificity showed a tendency to be lower in cirrhotic compared with non-cirrhotic patients, with a notably higher background liver uptake in cirrhosis (SUVmax 3.60 vs. 1.3, p < 0.001), resulting in lower TBR values (3.7 vs. 7.0, p < 0.001). A strong correlation between SUVmax and tumor size was seen in non-cirrhotic HCC, while a moderate association between SUVmax and PIVKA-II levels was observed in cirrhotic patients. Conclusions:68Ga-FAPI-04 PET/CT demonstrates high sensitivity for HCC detection and may serve as a complementary imaging modality, particularly when interpreted through conventional cross-sectional imaging. Image interpretation in cirrhotic livers may be challenging due to increased background uptake and reduced TBR. Associations between PET-derived parameters, tumor size, and serum PIVKA-II levels should be considered hypothesis-generating and require validation in larger, multicenter studies with clinical outcome data. Full article
(This article belongs to the Collection Nuclear Medicine and Molecular Imaging Technology)
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14 pages, 1015 KB  
Article
False-Positive PET Uptake in Left Atrial Appendage Closure Devices Due to Postoperative Inflammatory Response
by Marta Hernández-Meneses, Guillermo Cuervo, Marta Tormo-Ratera, Manuel Castellà, Marta Maristany, José María Tolosana, Eduard Quintana, Carlos Falces, Barbara Vidal, Cristina Garcia-de-la-Mària, María-Alexandra Cañas, Jaime Llopis, Asunción Moreno, José María Miró, Andrés Perissinotti, on behalf of the Hospital Clinic Endocarditis Study Group  and Clínic Barcelona Nuclear Medicine Group
Diagnostics 2026, 16(2), 200; https://doi.org/10.3390/diagnostics16020200 - 8 Jan 2026
Viewed by 385
Abstract
Background: Positron emission tomography (PET) is a valuable tool in the diagnosis of cardiovascular infections. However, increased radiotracer uptake can also be observed in non-infectious inflammatory processes, leading to potential false positives. This study analyzed the uptake related to left atrial appendage closure [...] Read more.
Background: Positron emission tomography (PET) is a valuable tool in the diagnosis of cardiovascular infections. However, increased radiotracer uptake can also be observed in non-infectious inflammatory processes, leading to potential false positives. This study analyzed the uptake related to left atrial appendage closure devices (LAACD—AtriClip®) to determine its association with infectious or inflammatory processes. Methods: We retrospectively analyzed 28 PET/CT scans from 20 patients with implanted LAACDs: 24 using 18F-fluorodeoxyglucose (FDG) and 4 using 18F-Choline (CHO). Clinical, laboratory, and imaging data were reviewed, and PET uptake was measured semi-quantitatively. All patients had at least 12 months of follow-up after PET imaging to assess for evidence of device-related infection. Results: Homogeneous PET uptake in the LAACD was observed in 93% (26/28) of the PET studies, regardless of the radiotracer used, clinical indication, or time since implantation. Clinical follow-up and laboratory findings revealed no signs of infection related to the LAACD in any case. SUV ratios did not differ significantly between the three PET indication groups (infection, neoplasia, or other; p = 0.46), nor between scans performed in patients with and without other confirmed infections unrelated to the LAACD (p = 0.37). Conclusions: FDG and CHO uptake in LAACDs appears to be a consistent and reproducible finding, most likely reflecting a sterile inflammatory response postoperative inflammatory uptake rather than true infection. Clear recognition of this uptake pattern is important to prevent misinterpretation and reduce the risk of false-positive PET/CT results in patients evaluated for suspected cardiovascular infections. Full article
(This article belongs to the Special Issue Infective Endocarditis in Cardiac Prosthesis and Devices)
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26 pages, 353 KB  
Review
Nuclear Imaging in Renal Cell Carcinoma: Current Evidence and Clinical Applications
by Abdullah Al-Khanaty, Shane Qin, Carlos Delgado, David Hennes, Eoin Dinneen, David Chen, Lewis Au, Renu S. Eapen, Damien Bolton, Declan G. Murphy, Nathan Lawrentschuk, Gregory Jack, Daniel Moon, Michael S. Hofman and Marlon L. Perera
Cancers 2026, 18(2), 195; https://doi.org/10.3390/cancers18020195 - 7 Jan 2026
Viewed by 398
Abstract
Introduction: Radiotracer-based nuclear imaging, including positron emission tomography (PET) and single-photon emission computed tomography (SPECT), can complement conventional cross-sectional imaging in renal cell carcinoma (RCC) by providing biological characterisation of tumour metabolism, angiogenesis, hypoxia, and the tumour microenvironment. While computed tomography (CT) and [...] Read more.
Introduction: Radiotracer-based nuclear imaging, including positron emission tomography (PET) and single-photon emission computed tomography (SPECT), can complement conventional cross-sectional imaging in renal cell carcinoma (RCC) by providing biological characterisation of tumour metabolism, angiogenesis, hypoxia, and the tumour microenvironment. While computed tomography (CT) and magnetic resonance imaging (MRI) remain the diagnostic standard, accumulating evidence suggests that selected nuclear imaging techniques may offer incremental value in specific clinical scenarios. Methods: A narrative literature review was performed using PubMed, Embase, and Web of Science to identify preclinical, retrospective, and prospective studies evaluating PET and SPECT radiotracers in localised and metastatic RCC. Priority was given to meta-analyses, multicentre prospective trials, and studies with histopathological correlation. Results: [18F]fluorodeoxyglucose (FDG) PET/CT demonstrates limited sensitivity for primary renal tumours (pooled sensitivity of approximately 60%) but performs substantially better in metastatic and recurrent disease (pooled sensitivity and specificity of approximately 85–90%), where uptake correlates with tumour grade, progression-free survival, and overall survival. [99mTc]sestamibi SPECT/CT differentiates oncocytoma and hybrid oncocytic/chromophobe tumours from malignant RCC with pooled sensitivity and specificity of around 85–90%, supporting its role in evaluating indeterminate renal masses rather than staging. Prostate-specific membrane antigen (PSMA) PET/CT shows high detection rates in clear-cell RCC, particularly in metastatic disease, with reported sensitivities of approximately 85–90% and management changes in up to 40–50% of selected cohorts. Carbonic anhydrase IX (CAIX)-targeted PET/CT enables the biologically specific visualisation of clear-cell RCC, achieving sensitivities and specificities in the range of 85–90% in prospective phase II and III trials for primary tumour characterisation. Fibroblast activation protein inhibitor (FAPI) PET/CT demonstrates high tumour-to-background uptake in early RCC studies, but evidence remains preliminary, with small cohorts and recognised non-specific uptake in benign inflammatory and fibrotic conditions. Conclusions: Radiotracer-based nuclear imaging provides complementary, biology-driven insights in RCC that extend beyond anatomical assessment. While most modalities remain adjunctive or investigational and are not recommended for routine use, selective application in carefully chosen clinical scenarios may enhance tumour characterisation, prognostication, and personalised treatment planning. Full article
(This article belongs to the Section Methods and Technologies Development)
4 pages, 2634 KB  
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Fusion Imaging of 18F-FDG PET and MRI Identified an Inflammatory Esophageal Diverticulum in a Patient with Radioiodine-Refractory Differentiated Thyroid Cancer
by Jiamiao Yang, Peng Zhong, Jiahuan Yang, Xusen Yang and Libo Chen
Diagnostics 2026, 16(2), 188; https://doi.org/10.3390/diagnostics16020188 - 7 Jan 2026
Viewed by 176
Abstract
A radioiodine-refractory differentiated thyroid cancer patient with rising serum thyroglobulin (Tg) levels underwent 18F-FDG PET/CT scan, which showed a hypermetabolic region in the proximal segment of esophagus, leading to ambiguity in diagnosis. MRI was immediately added, and PET/MRI fusion image localized an [...] Read more.
A radioiodine-refractory differentiated thyroid cancer patient with rising serum thyroglobulin (Tg) levels underwent 18F-FDG PET/CT scan, which showed a hypermetabolic region in the proximal segment of esophagus, leading to ambiguity in diagnosis. MRI was immediately added, and PET/MRI fusion image localized an air-containing lesion interlinked with esophagus with enhanced T2 hyperintense mucosal signal, indicating an inflammatory esophageal diverticulum, which was subsequently verified by endoscopy. This case highlights the added value of PET/MRI image fusion in cases with inconclusive 18F-FDG PET/CT findings, requiring no additional tests and utilizing existing software, thereby minimizing the need for invasive procedures. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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11 pages, 567 KB  
Article
Tumor Characterization Using [18F]FDG PET Radiomics in a PD-L1-Positive NSCLC Cohort
by Bernadett Erzsébet Kálmán, Agnieszka Bos-Liedke, Dániel Dezső, Ewelina Kaminska, Mateusz Matusewicz, Ferenc Budán, Domokos Mathe, János Girán, Dávid Sipos, Éva Pusztai, Árpád Boronkai and Zsombor Ritter
Pharmaceuticals 2026, 19(1), 103; https://doi.org/10.3390/ph19010103 - 7 Jan 2026
Viewed by 219
Abstract
Background: Durvalumab consolidation following radiochemotherapy is now the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). [18F]FDG PET/CT offers valuable insights not just for staging but also for tumor characterization via radiomics, which can potentially predict histology, [...] Read more.
Background: Durvalumab consolidation following radiochemotherapy is now the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). [18F]FDG PET/CT offers valuable insights not just for staging but also for tumor characterization via radiomics, which can potentially predict histology, immunophenotype, and prognosis. Methods: We conducted a retrospective analysis of [18F]FDG PET/CT scans from stage IIIA–IIIB NSCLC patients treated at the Clinical Centre, University of Pécs. All biopsy samples were classified histologically (squamous vs. adenocarcinoma) and tested for PD-L1. Lung tumors were segmented using MEDISO InterViewTM FUSION software (version 3.12.002.0000). with an SUVmax threshold of four. Imaging features were extracted and compared based on histology, PD-L1 status, and neutrophil-to-lymphocyte ratio (NLR)-based prognosis groups. Statistical analyses were performed with Jamovi (v2.6.44), using Shapiro–Wilk, t-test/ANOVA, Mann–Whitney/Kruskal–Wallis, or Chi-square tests as appropriate. Results: Fifty-six patients were included (38 PD-L1-positive, 18 -negative). Among PD-L1-positive cases, poor versus good NLR prognosis groups differed in maximum diameter (p = 0.046), short-zone emphasis (p = 0.026), and zone-length non-uniformity (p = 0.027). Focusing on PD-L1-positive squamous carcinoma, maximum diameter, metabolic tumor volume, busyness, and coarseness showed significant differences (all p < 0.05). SUVmax, mean SUV, SUVpeak, and complexity were higher in squamous than in adenocarcinoma subtypes. PD-L1-positive and -negative squamous tumors differed in zone percentage (p = 0.039) and long-zone high gray-level emphasis (p = 0.024), while no significant differences were observed among adenocarcinomas. Conclusions: [18F]FDG PET/CT radiomics showed potential for differentiating NSCLC histological subtypes and for identifying PD-L1-associated imaging patterns in squamous cell carcinoma. In addition, certain metabolic features were associated with NLR-based prognostic groups in PD-L1-positive patients. Full article
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21 pages, 687 KB  
Review
Radiolabelled FAPI Radiotracers in Oncology: A Comprehensive Review of Current Diagnostic and Emerging Therapeutic Applications
by Jolanta Czuczejko, Bogdan Małkowski, Jarosław Nuszkiewicz, Iga Hołyńska-Iwan, Paweł Waśniowski, Katarzyna Mądra-Gackowska, Wiktor Dróżdż and Karolina Szewczyk-Golec
Pharmaceuticals 2026, 19(1), 89; https://doi.org/10.3390/ph19010089 - 2 Jan 2026
Viewed by 477
Abstract
Background/Objectives: Fibroblast activation protein (FAP), which is abundantly expressed in cancer-associated fibroblasts (CAFs) across various epithelial malignancies, has emerged as a promising target for molecular imaging and radionuclide therapy. Although several reviews have addressed FAP-targeted diagnostics, a comprehensive synthesis integrating molecular biology, [...] Read more.
Background/Objectives: Fibroblast activation protein (FAP), which is abundantly expressed in cancer-associated fibroblasts (CAFs) across various epithelial malignancies, has emerged as a promising target for molecular imaging and radionuclide therapy. Although several reviews have addressed FAP-targeted diagnostics, a comprehensive synthesis integrating molecular biology, diagnostic performance, and early therapeutic development remains limited. This review summarises the current evidence on radionuclide-labelled FAP inhibitors (FAPIs), with particular emphasis on their diagnostic utility, emerging therapeutic applications, and the structural features that shape their biological behaviour. Methods: A structured literature search was conducted across PubMed, Scopus, and Web of Science, focusing on FAPI-based imaging and therapy. Results: Diagnostic studies consistently demonstrate high tumour-to-background contrast for [68Ga]Ga and [18F]-labelled FAPI radiotracers, particularly in tumours with prominent stromal components such as pancreatic, colorectal, breast, and head and neck cancers. FAPI PET/CT often surpasses [18F]FDG in lesion conspicuity in the brain, liver, and peritoneum. Therapeutic evidence shows encouraging tumour retention and safety profiles for agents such as [177Lu]Lu-FAP-2286 and [90Y]Y-FAPI-46, while α-emitting radiotracers (e.g., [225Ac]Ac-FAPI-04) demonstrate potent antitumor effects in preclinical models. Conclusions: Radiolabelled FAPI radiotracers hold significant potential as dual diagnostic and therapeutic agents, particularly for desmoplastic tumours with high CAF content. Nonetheless, clinical evidence remains in its early stages, and substantial questions persist regarding dosimetry, intertumoral variability in FAP expression, and optimal ligand selection for therapy. Continued development of next-generation FAPI constructs, along with well-designed prospective trials, will be crucial in defining the future role of FAPI-based theranostics in oncology. Full article
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12 pages, 657 KB  
Article
Prognostic Value of Treatment-Related Body Composition Changes in Metastatic NSCLC Receiving Nivolumab
by Erkam Kocaaslan, Ali Kaan Güren, Fırat Akagündüz, Ahmet Demirel, Mustafa Alperen Tunç, Burak Paçacı, Yeşim Ağyol, Pınar Erel, Abdüssamed Çelebi, Selver Işık, Ezgi Çoban, Nazım Can Demircan, Salih Özgüven, Zeynep Ceren Balaban Genç, Nargiz Majidova, Nadiye Sever, Murat Sarı, Osman Köstek and İbrahim Vedat Bayoğlu
Medicina 2026, 62(1), 98; https://doi.org/10.3390/medicina62010098 - 2 Jan 2026
Viewed by 255
Abstract
Background and Objectives: This study aimed to evaluate the prognostic impact of baseline body composition measurements and changes in muscle and adipose tissue during treatment on overall survival (OS) in metastatic non-small cell lung cancer (NSCLC) patients treated with nivolumab. Materials and Methods: [...] Read more.
Background and Objectives: This study aimed to evaluate the prognostic impact of baseline body composition measurements and changes in muscle and adipose tissue during treatment on overall survival (OS) in metastatic non-small cell lung cancer (NSCLC) patients treated with nivolumab. Materials and Methods: Eighty-eight metastatic NSCLC patients who were initiated on nivolumab between January 2022 and December 2024 were retrospectively analyzed. Body composition parameters were derived from baseline and 3-month 18F-FDG PET/CT scans at the L3 level, including psoas muscle index (PMI), skeletal muscle index (SMI), intramuscular adipose content (IMAC), and subcutaneous fat density (SFD). Treatment-related changes in body composition were evaluated, and survival analyses were performed using Kaplan–Meier estimates and Cox regression models. Results: Overall, 34.1% (n = 30) of patients were classified as sarcopenic. Median OS was significantly longer in non-sarcopenic patients (19 months vs. 5 months, p < 0.001). In univariate analysis, older age, higher comorbidity burden, liver metastasis, baseline sarcopenia, and adverse treatment-related changes in muscle and nutritional parameters were found to be associated with OS. In multivariate analysis, only unfavorable changes in skeletal muscle (ΔSMI; HR 3.39, p = 0.003) and subcutaneous fat radiodensity (ΔSFD; HR 2.45, p = 0.02) remained independent adverse prognostic factors. Baseline body composition parameters did not maintain their independence in multivariate models. Conclusions: Our study demonstrates that muscle loss or insufficient gain and unfavorable changes in subcutaneous fat radiodensity during nivolumab treatment more strongly predict overall survival compared to baseline measurements. These findings highlight the clinical importance of monitoring dynamic body composition throughout treatment, rather than static assessments, in NSCLC patients receiving immunotherapy. Full article
(This article belongs to the Section Oncology)
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17 pages, 2776 KB  
Article
The Prognostic Value of Biomarkers Identified by [18F]FDG-PET/CT in Patients with High-Risk Melanoma Treated with Adjuvant Immunotherapy
by Anne-Line Mayland Madsen, Oke Gerke, Christina H. Ruhlmann, Malene Grubbe Hildebrandt and Sambavy Nadaraja
Diagnostics 2026, 16(1), 79; https://doi.org/10.3390/diagnostics16010079 - 25 Dec 2025
Viewed by 499
Abstract
Background: Adjuvant anti-PD-1 therapy improves recurrence-free survival (RFS) in high-risk melanoma, but many patients experience adverse events. 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography with computed tomography [18F]FDG-PET/CT has been proposed to identify biomarkers that may predict outcome of treatment. Objectives [...] Read more.
Background: Adjuvant anti-PD-1 therapy improves recurrence-free survival (RFS) in high-risk melanoma, but many patients experience adverse events. 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography with computed tomography [18F]FDG-PET/CT has been proposed to identify biomarkers that may predict outcome of treatment. Objectives: The aim of this register-based study was to investigate the prognostic value of immune-related adverse events (irAEs), spleen-to-liver ratio (SLR), and bone marrow-to-liver ratio (BLR), detected by [18F]FDG-PET/CT. Methods: This retrospective, register-based cohort study included 122 patients with radically resected stage III–IV melanoma treated with adjuvant anti-PD-1. Patient data were extracted from a Danish register, and measurements for SLR and BLR were made using an AI model. Cox regression models were made on irAEs and BLR to assess associations with RFS and overall survival (OS). Results: Over half of the patients experienced recurrence, and one quarter died during follow-up of 4 ¾ years. Seventy-four percent exhibited at least one PET-detected irAE. This study found no association between irAEs and OS. Regarding RFS, our findings suggest an increased risk of recurrence for the presence of irAEs within the first 1.5 years of follow-up (HR: 2.93, CI: 1.10–7.84, p = 0.032). BLR and SLR were not associated with RFS or OS in multivariable models. Conclusions: This study did not confirm the findings of a positive association between irAEs and survival found in previous studies. PET-detected irAEs were common in the study population, but did not predict OS, while early-onset irAEs were linked to increased recurrence risk. Neither SLR nor BLR demonstrated prognostic value. Further research is needed to clarify the clinical utility of PET-derived biomarkers, especially in the adjuvant setting. Full article
(This article belongs to the Special Issue Advances in Inflammation and Infection Imaging: 2nd Edition)
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12 pages, 5085 KB  
Case Report
Whole Genome Sequencing of Clinical Mycobacterium bovis BCG in Disseminated Infection with Mycotic Aneurysm and ARDS After Intravesical Therapy: A Case Report
by Yuta Nakagawa, Chie Yamamoto, Hidetake Kawajiri, Makoto Watanabe, Tomomi Yamada, Yukiji Yamada, Daisuke Kambayashi, Keitaro Furukawa, Ryosuke Hamashima, Tetsuhiro Yamano, Tohru Inaba, Kunihiko Kooguchi, Shinichiro Oda, Satoshi Mitarai and Yoko Nukui
Int. J. Mol. Sci. 2026, 27(1), 238; https://doi.org/10.3390/ijms27010238 - 25 Dec 2025
Viewed by 353
Abstract
Intravesical Bacillus Calmette–Guérin (iBCG) immunotherapy is the standard adjuvant treatment of non-muscle-invasive bladder cancer (NMIBC). Among the potential complications, cases of mycotic aneurysms and acute respiratory distress syndrome (ARDS) are rare but can be life-threatening. Because prior reports have not included whole-genome sequencing [...] Read more.
Intravesical Bacillus Calmette–Guérin (iBCG) immunotherapy is the standard adjuvant treatment of non-muscle-invasive bladder cancer (NMIBC). Among the potential complications, cases of mycotic aneurysms and acute respiratory distress syndrome (ARDS) are rare but can be life-threatening. Because prior reports have not included whole-genome sequencing (WGS) of clinical Mycobacterium bovis BCG (M. bovis BCG) isolates to assess whether the infecting strain acquires mutations in vivo, we performed WGS in a severe disseminated iBCG-related infection. A 72-year-old man with bladder cancer underwent iBCG instillation. Twelve months after the final instillation, the patient developed an abdominal aortic aneurysm, which was detected and treated with endovascular aneurysm repair (EVAR). Two months later, the patient presented with fever, abdominal pain, and septic shock. Contrast-enhanced computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) showed rapid aneurysm enlargement. Ziehl–Neelsen staining and PCR of aortic material identified M. bovis BCG. Direct PCR on BAL fluid and urine was negative; however, BAL and urine culture subsequently grew M. bovis BCG, and PCR performed on the culture isolate confirmed M. bovis BCG. Despite combined antituberculosis triplet therapy (isoniazid, rifampicin, and ethambutol), the patient developed ARDS, which gradually improved after surgical management. WGS (with >96% genome coverage) showed the isolate was highly concordant with the vaccine strain and lacked additional virulence-associated mutations, including in esxM. This case illustrates that severe systemic iBCG-related complications can occur without detectable in vivo acquisition of virulence-enhancing mutations; however, interpretation is limited by the single-case design and the absence of host genetic susceptibility testing. Our findings underscore the need for prolonged vigilance regarding late-onset vascular and pulmonary complications after iBCG, and highlight the importance of early multidisciplinary management. Full article
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28 pages, 765 KB  
Systematic Review
Radiomic-Based Machine Learning Classifiers for HPV Status Prediction in Oropharyngeal Cancer: A Systematic Review and Meta-Analysis
by Anna Luíza Damaceno Araújo, Luiz Paulo Kowalski, Alan Roger Santos-Silva, Brendo Vinícius Rodrigues Louredo, Cristina Saldivia-Siracusa, Otávio Augusto A. M. de Melo, Deivid Cabral, Andrés Coca-Pelaz, Orlando Guntinas-Lichius, Remco de Bree, Pawel Golusinski, Karthik N. Rao, Robert P. Takes, Nabil F. Saba and Alfio Ferlito
Diagnostics 2026, 16(1), 68; https://doi.org/10.3390/diagnostics16010068 - 24 Dec 2025
Viewed by 511
Abstract
Background: The aim of the present systematic review (SR) is to compile evidence regarding the use of radiomic-based machine learning (ML) models for predicting human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) patients and to assess their reliability, methodological frameworks, and [...] Read more.
Background: The aim of the present systematic review (SR) is to compile evidence regarding the use of radiomic-based machine learning (ML) models for predicting human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) patients and to assess their reliability, methodological frameworks, and clinical applicability. The SR was conducted following PRISMA 2020 guidelines and registered in PROSPERO (CRD42025640065). Methods: Using the PICOS framework, the review question was defined as follows: “Can radiomic-based ML models accurately predict HPV status in OPSCC?” Electronic databases (Cochrane, Embase, IEEE Xplore, BVS, PubMed, Scopus, Web of Science) and gray literature (arXiv, Google Scholar and ProQuest) were searched. Retrospective cohort studies assessing radiomics for HPV prediction were included. Risk of bias (RoB) was evaluated using Prediction model Risk Of Bias ASsessment Tool (PROBAST), and data were synthesized based on imaging modality, architecture type/learning modalities, and the presence of external validation. Meta-analysis was performed for externally validated models using MetaBayesDTA and RStudio. Results: Twenty-four studies including 8627 patients were analyzed. Imaging modalities included computed tomography (CT), magnetic resonance imaging (MRI), contrast-enhanced computed tomography (CE-CT), and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). Logistic regression, random forest, eXtreme Gradient Boosting (XGBoost), and convolutional neural networks (CNNs) were commonly used. Most datasets were imbalanced with a predominance of HPV+ cases. Only eight studies reported external validation results. AUROC values ranged between 0.59 and 0.87 in the internal validation and between 0.48 and 0.91 in the external validation results. RoB was high in most studies, mainly due to reliance on p16-only HPV testing, insufficient events, or inadequate handling of class imbalance. Deep Learning (DL) models achieved moderate performance with considerable heterogeneity (sensitivity: 0.61; specificity: 0.65). In contrast, traditional models provided higher, more consistent performance (sensitivity: 0.72; specificity: 0.77). Conclusions: Radiomic-based ML models show potential for HPV status prediction in OPSCC, but methodological heterogeneity and a high RoB limit current clinical applicability. Full article
(This article belongs to the Special Issue Clinical Diagnosis of Otorhinolaryngology)
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14 pages, 3060 KB  
Article
Assessment of the Diagnostic Value of [68Ga]Ga-FAPI-04 and [18F]FDG PET in a PHMG-p-Induced Pulmonary Fibrosis Murine Model
by So Young Kim, Jun Young Park, Ye Lim Cho and Won Jun Kang
Diagnostics 2026, 16(1), 10; https://doi.org/10.3390/diagnostics16010010 - 19 Dec 2025
Viewed by 584
Abstract
Background/Objectives: Pulmonary fibrosis is a progressive and fatal lung disease with limited diagnostic and therapeutic options. Fibroblast activation protein (FAP) has emerged as a promising molecular imaging target for the non-invasive assessment of fibrotic activity. This study aimed to evaluate the diagnostic feasibility [...] Read more.
Background/Objectives: Pulmonary fibrosis is a progressive and fatal lung disease with limited diagnostic and therapeutic options. Fibroblast activation protein (FAP) has emerged as a promising molecular imaging target for the non-invasive assessment of fibrotic activity. This study aimed to evaluate the diagnostic feasibility of [68Ga]Ga-FAP inhibitor (FAPI) and [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) for imaging pulmonary fibrosis in a mouse model. Methods: A pulmonary fibrosis model was established by intratracheal administration of polyhexamethylene guanidine-phosphate (PHMG-p) to C57BL/6 mice. Fibrosis severity was quantified by the Ashcroft scoring system using hematoxylin and eosin and Masson’s trichrome staining and evaluated by computed tomography (CT) imaging at 7, 14, and 21 days after PHMG-p exposure. PET imaging was performed, and ex vivo biodistribution was assessed after injection of [68Ga]Ga-FAPI-04 and [18F]FDG. Results: Histological analysis and Ashcroft scoring revealed greater fibrosis severity in the PHMG-p-treated group. Western blot analysis demonstrated upregulation of FAP expression after PHMG-p exposure. CT showed increased mean lung density, while [68Ga]Ga-FAPI-04 PET revealed significantly elevated pulmonary uptake of [68Ga]Ga-FAPI-04 in the PHMG-p-treated group compared with the controls. [18F]FDG PET imaging also showed higher uptake of [18F]FDG in the PHMG-p-treated group than in the controls. Ex vivo biodistribution confirmed greater [68Ga]Ga-FAPI-04 accumulation in the lungs of PHMG-p-treated mice. Conclusions: [68Ga]Ga-FAPI-04 PET serves as a sensitive imaging biomarker for evaluation of fibrotic activity in PHMG-p-induced pulmonary fibrosis and complements [18F]FDG PET for assessing disease progression and therapeutic response. Full article
(This article belongs to the Special Issue New Advances in Chest Imaging)
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