Search Results (1,215)

Head and neck cancers account for approximately 3.0% of all new cancer diagnoses. 18F-FDG PET/CT plays an important role in the initial staging of these cancers, especially in the detection of nodal and distant metastatic disease, outperforming conventional imaging techniques. It helps identify occult primary tumors and synchronous second primary malignancies. PET/CT findings can lead to treatment plan alterations both in surgical and primary or adjuvant chemoradiation plans. High negative predictive value at treatment response assessment provides valuable prognostic implications. PET/CT can predict outcomes at baseline and during or after treatment. Full article

Background/Objectives: [¹⁸F]FDG-PET is often used for staging thymic epithelial tumours (TETs). However, its prognostic role remains uncertain. The aim of this present systematic review and meta-analysis is to assess the prognostic value of baseline [¹⁸F]FDG-PET-derived semiquantitative parameters in predicting progression-free survival (PFS) in patients with TETs. Methods: A systematic review and meta-analysis were conducted according to PRISMA guidelines. PubMed, Embase, and Scopus databases were searched up to 30 May 2025. Studies evaluating the prognostic impact of [¹⁸F]FDG-PET parameters on PFS in TETs were included. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Results: Six retrospective studies involving 593 patients were included. Maximum standardized uptake value (SUVmax), analysed as a continuous variable in four studies, significantly predicted worse PFS (HR: 1.18, 95% CI: 1.08–1.29, p < 0.001), with high inter-study heterogeneity (I² = 79.7%). When dichotomized (two studies), higher SUVmax was associated with significantly poorer PFS (HR: 9.00, 95% CI: 2.93–27.71). Similarly, mean SUV (SUVmean) as a continuous predictor was also significantly associated with impaired PFS (HR: 1.41, 95% CI: 1.25–1.59), but only two studies assessed this parameter. Conversely, metabolic tumour volume (MTV) and total lesion glycolysis (TLG), both assessed as continuous prognosticators, did not show a significant prognostic value. Notably, in both MTV and TLG analyses, two studies contributed a weight of 0%, reflecting limited precision and highlighting the need for larger data. Conclusions: Baseline [¹⁸F]FDG-PET parameters such as SUVmax and SUVmean showed a potential prognostic value in patients with TETs. However, these results are based on a limited number of retrospective studies with significant heterogeneity. Prospective multicentre investigations are necessary to confirm the potential role of [¹⁸F]FDG-PET for risk stratification in TETs. Full article

The rapid advancements in computer processing, algorithmic development, and the availability of large-scale datasets have positioned Artificial Intelligence (AI) as a valuable tool across multiple domains, including Medicine. In the field of Nuclear Medicine neuroimaging, with Positron Emission Tomography (PET), AI has demonstrated significant potential in improving diagnostic accuracy for neurodegenerative cognitive disorders. This is especially relevant for the early diagnosis, preclinical detection, and prediction of disease progression in Alzheimer’s disease (AD), the most prevalent form of cognitive impairment in individuals over 65 years of age. This narrative review aims to synthesize current advances, explore future directions, and highlight outstanding challenges in the application of Artificial Intelligence to PET imaging for the clinical management of Alzheimer’s disease, with particular focus on three key modalities: ¹⁸F-FDG PET, Amyloid PET, and Tau PET. Full article

Intraosseous hibernoma (IOH) is a rare benign tumor composed of brown adipose tissue within the bone, frequently mimicking metastatic lesions and leading to diagnostic challenges. This systematic review aimed to consolidate and analyze all published IOH cases to improve recognition and inform management. A comprehensive literature search was conducted in PubMed, Web of Science, Scopus, Google Scholar, and the Cochrane Library from database inception to March 2025. Studies were eligible for inclusion if they reported histopathologically confirmed cases of intraosseous hibernoma (IOH) in human patients. A total of 62 cases from 30 studies were included. The mean age was 59.2 years, with a female predominance. Lesions were most frequently located in the pelvis and spine and were typically identified incidentally during cancer staging or imaging performed for unrelated indications. Imaging often revealed sclerotic patterns on computed tomography (CT), hyperintense signals on magnetic resonance imaging (MRI) T2-weighted and short tau inversion recovery (STIR) sequences, and mild to moderate uptake on ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT). Immunohistochemistry consistently showed S100 protein positivity. Most patients underwent biopsy and were managed conservatively, with no cases of malignant transformation reported. IOH is a benign entity with distinctive radiologic and immunohistochemical features that may mimic malignancy. Awareness of its presentation can reduce misdiagnosis and unnecessary interventions, supporting biopsy-based confirmation and conservative management in most cases. Full article

Objective: To identify distinctive 18F-FDG positron emission tomography (PET)/computer tomography (CT) features of gastric-type endocervical adenocarcinoma (GAS) that differentiate it from squamous cell carcinoma (SCC) and usual-type endocervical adenocarcinoma (UEA), as well as to correlate these findings with pathological characteristics. Methods: Patients treated between December 2018 and December 2024 were retrospectively reviewed. The study included 12 GAS, 48 SCC, and 30 UEA cases. Evaluated parameters included tumor morphology, cystic components, uterine cavity fluid, N/M staging, tumor diameter, the cervical lesion maximum standardized uptake value (SUVmax), and the tumor-to-liver maximum standardized uptake ratio (T/L SUVmax). Results: GAS predominantly exhibited diffuse infiltrative growth (11/12), in contrast to mass-like growth observed in SCC (37/48) and UEA (24/30) (both p < 0.001). Cystic components, uterine cavity fluid, and peritoneal metastasis occurred significantly more frequently in GAS (12/12, 11/12, 5/12, respectively) compared to SCC and UEA (all p < 0.001). Elevated CA19-9 levels were more common in GAS (9/12) compared with SCC (p < 0.001). Tumor diameter did not differ significantly among the groups (p > 0.05). SUVmax and T/L SUVmax values were significantly lower in GAS (7.5 ± 3.8 and 2.5 ± 1.6, respectively) than in UEA (19.1 ± 11.4 and 5.7 ± 3.4) and SCC (17.4 ± 6.7 and 5.5 ± 2.6) (all p < 0.001). Conclusion: The clinical characteristics of GAS include infiltrative tumor growth, fluid accumulation in the uterine cavity, frequent formation of microcystic or macrocystic components, peritoneal metastasis, and elevated CA19-9 levels. In this cohort, SUVmax and T/L SUVmax values in GAS were significantly lower than those observed in SCC and UEA. Full article

Background/Objectives: The neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, is a known predictor of cardiovascular disease and overall mortality. We examined the relationship between the NLR and the metabolic activity of hematopoietic organs and visceral fat, and their association with the risk of atherosclerotic cardiovascular disease (ASCVD) in an asymptomatic healthy population. Methods: We retrospectively analyzed individuals who underwent F-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) as part of their health check-ups. Metabolic activity was quantified using standardized uptake values (SUVs) from the lumbar vertebral bone marrow, spleen, visceral, and subcutaneous fat, normalized to target-to-background ratios (TBRs) using the superior vena cava. NLR was calculated from absolute neutrophil and lymphocyte counts. Correlations between NLR, clinical parameters, organ TBRs, and ASCAD risk were analyzed. Results: Among 303 participants from three hospitals, the median NLR was 1.5 (range: 0.5–5.55). NLR showed weak correlation with the TBRs of bone marrow, visceral fat, and subcutaneous fat, as well as high-density lipoprotein cholesterol and body mass index (BMI). In logistic regression analysis adjusted for age and sex, BMI and the TBRs of bone marrow and visceral fat were independent predictors of elevated NLR (≥ 1.5). When integrating these parameters, NLR demonstrated strong predictive performance for identifying a high ASCVD risk (≥20% over 10 years), with an area under the curve of 0.826. Conclusions: In an asymptomatic healthy population, NLR is associated with FDG metabolic parameters of hematopoietic organs and adipose tissue. These combined measures may serve as valuable marker for identifying individuals at elevated ASCVD risk. Full article

Objective: The high expression of prostate-specific membrane antigen (PSMA) associated with neovascularization in non-prostatic malignant tumors and metastatic lesions has been documented in many studies. By taking advantage of the absence of PSMA-related background activity in brain tissue, in recent years, PSMA has been used for the imaging of glial tumors, especially for postoperative follow-up. The aim of this prospective study was to investigate the diagnostic value of ⁶⁸Ga-PSMA-11 PET/CT by comparing ⁶⁸Ga-PSMA-11 PET/CT, ¹⁸F-FDG PET/CT, and MRI findings in patients with brain metastases (BM). Materials and Method: In this prospective study, 27 cases, 11 female and 16 male, with a mean age of 59.48 ± 12.21 years, were included. Patients diagnosed with BM on ¹⁸F-FDG PET/CT or CT/MRI at initial diagnosis or in the follow-up period were included in the study. PET findings of BM lesions obtained from ¹⁸F-FDG and ⁶⁸Ga-PSMA-11 PET/CT imaging, demographic characteristics, histopathological data of the primary foci, and other clinical features were evaluated together. Results: Twenty-four (89%) patients were included in the study for restaging, two (7%) patients for local recurrence assessment, and one (4%) patient for local recurrence and suspicion of additional lesions. The indications for ¹⁸F-FDG PET/CT were breast carcinoma for 37% (n:10), followed by lung carcinoma for 26% (n:7), colorectal adenocarcinoma for 14% (n:4), squamous cell larynx carcinoma for 7% (n:2), gastric signet ring cell carcinoma for 4% (n:1), pancreatic NET3 for 4% (n:1), thyroid papillary carcinoma for 4% (n:1), and malignant melanoma for 4% (n:1). In total, 26/27 included patients had PSMA-positive brain metastases but only one patient had PSMA-negative brain metastases with ⁶⁸Ga-PSMA-11 PET/CT imaging. This patient was followed with a diagnosis of primary larynx squamous carcinoma and had a mass suspected of brain metastases. Further tests and an MRI revealed that the lesion in this patient was a hemorrhagic metastasis. The smallest metastatic focus on ⁶⁸Ga-PSMA-11 PET/CT imaging was 0.22 cm, also confirmed by MRI (range: 0.22–2.81 cm). The mean ± SD SUVmax of the BM lesions was 17.9 ± 8.6 and 6.8 ± 5.2 on ¹⁸F-FDG PET/CT and ⁶⁸Ga-PSMA-11 PET/CT imaging, respectively. Metastatic foci that could not be detected by ¹⁸F-FDG PET/CT imaging were successfully detected with ⁶⁸Ga-PSMA-11 PET/CT imaging in 11 cases (42%). The distribution and number of metastatic lesions observed on cranial MRI and ⁶⁸Ga-PSMA-11 PET/CT were compatible with each other for all patients. Immunohistochemical staining was performed in the primary tumor of 10 (38%) cases, and positive IHC staining with PSMA was detected in 5 patients. In addition, positive IHC staining with PSMA was detected in all of the four surgically excised brain metastatic tumor foci. Conclusions: In this study,⁶⁸Ga-PSMA-11 PET/CT appears to be superior to ¹⁸F-FDG in detecting BM from various tumors, largely due to its high expression associated with neovascularization and the absence of PSMA expression in normal brain parenchyma. This lack of physiological uptake in healthy brain tissue provides excellent tumor-to-background contrast, further supporting the advantage of ⁶⁸Ga-PSMA-11 over ¹⁸F-FDG for BM imaging. However, larger studies are required to confirm these findings, particularly through comparisons across tumor types and histopathological subgroups, integrating PSMA immunohistochemistry (IHC) scores with ⁶⁸Ga-PSMA-11 uptake levels. Beyond its diagnostic potential, our results may also inform PSMA-targeted therapeutic strategies, offering new perspectives for the management of patients with brain metastases from diverse primary tumors. Full article

Objectives: Cardiac involvement in scleroderma due to myocardial inflammation and fibrosis is associated with poor outcomes, but there is lack of consensus on its investigation and treatment. In this prospective pilot study, we aimed to assess the cardiac uptake of 18F-FDG-PET/CT in suspected scleroderma cardiomyopathy. Methods: The Scleroderma Heart study involved 16 patients with cardiac scleroderma but no coronary artery disease. 18F-FDG-PET/CTs were performed, and the patients with a positive scan were offered a second 18F-FDG-PET/CT scan after 6–9 months. The clinical characteristics and clinical outcomes (all-cause mortality) were compared between the patients with positive and negative 18F-FDG-PET/CT scans. Results: Of the 16 included patients, 8 (50%) had positive myocardial uptake on the 18F-FDG-PET/CT, 2 of whom showed a pattern consistent with cardiac involvement in scleroderma, while 6 patients more likely had physiological uptake. Over a mean follow-up of 603.3 days, all-cause mortality occurred in six patients (37.5%), and the mortality was similar between the two groups. Five patients with repeat 18F-FDG-PET/CTs showed stable or increased FDG uptake despite immunosuppression. Conclusions: To the best of our knowledge, this is the first study to investigate 18F-FDG-PET/CT in scleroderma patients with suspected cardiac involvement. The cardiac PET showed limited clinical utility due to frequent physiological uptake and lack of correlation with the treatment response. Further studies with larger cohorts and standardised interpretation criteria are needed before cardiac PET can be recommended for routine clinical use in scleroderma cardiomyopathy. Full article

The purpose was to determine the ability of 18-fluorodeoxyglucose (18F-FDG) positron emission tomography–computed tomography (PET-CT) scans performed within 24 h of percutaneous image-guided ablation of primary and metastatic malignancies to predict ablation effectiveness and local tumor progression (LTP). This single-center retrospective review included patients who underwent image guided ablation (microwave ablation (MWA), cryoablation, or irreversible electroporation (IRE)) between August 2018 and February 2024 for primary and metastatic malignancies. The primary outcome measure encompassed correlating post-ablation 18F-FDG PET-CT findings with LTP development per tumor, assessed using the chi-square test. The secondary outcome measure was local tumor progression-free survival (LTPFS) per tumor, evaluated using the Kaplan–Meier survival curves, and potential confounders were identified in multivariable analysis utilizing Cox proportional hazards regression models. A total of 132 patients, who underwent 159 procedures for 224 tumors, were included. During follow-up, LTP developed in 120 out of 224 tumors (53.6%). The presence of residual nodular 18F-FDG avidity on PET-CT within 24 h after the ablation significantly correlated with the development of LTP at follow-up imaging (p < 0.001). The positive predictive value of nodular 18F-FDG avidity was 86.7%. In multivariable analysis, the hazard ratio (HR) for 18F-FDG avidity was 2.355 (95% CI 1.614–2.647; p < 0.001). The presence of 18F-FDG avidity on PET-CT within 24 h after the ablation was highly correlated with development of LTP and decreased LTPFS. The detection of residual tumor tissue may allow early re-treatments, especially in tumors with nodular uptake, contributing to increased LTPFS. Full article

Background: Intermittent fasting (IF) is emerging as a promising non-pharmacological intervention in oncology, with the potential to modulate key biological processes including metabolic reprogramming, inflammation, autophagy, and immune function, particularly through the PI3K/AKT/mTOR pathway. However, translating IF into clinical practice requires robust tools to monitor its biological impact and therapeutic effectiveness. Objective: This narrative review aims to present and critically evaluate current diagnostic and monitoring strategies that can support the safe and effective integration of IF into oncological care. Methods: A comprehensive literature search was conducted across PubMed/Medline, Science Direct, Scopus, Wiley Online Library, and Google Scholar using a combination of free-text and MeSH terms related to intermittent fasting, oncology, biomarkers, immunophenotyping, metabolic pathways, gut microbiome, and diagnostic imaging. Results: Two principal categories of monitoring objectives were identified. The first—mechanistic monitoring—focuses on elucidating IF-induced biological effects, including modulation of insulin/IGF-1 signaling, oxidative stress reduction, autophagy activation, immune reprogramming, and microbiome alterations. Advanced research tools such as single-cell RNA sequencing, proteomics, metabolomics, and circulating tumor DNA (ctDNA) assays offer high-resolution insights but currently remain limited to preclinical or translational settings due to cost and complexity. The second—clinical response monitoring—assesses IF’s impact on treatment outcomes, including chemotherapy and immunotherapy response, toxicity reduction, tumor dynamics, and maintenance of nutritional and functional status. This requires clinically validated, accessible, and interpretable diagnostic tools. Conclusions: A dual-layered monitoring framework that integrates both mechanistic insights and clinical applicability is essential for the personalized implementation of IF in oncology. Although preliminary findings are promising, large-scale randomized trials with standardized protocols are necessary to confirm the efficacy, safety, and feasibility of IF in routine oncological care. The integration of IF with modern diagnostics may ultimately contribute to a more individualized, biologically informed cancer treatment paradigm. Full article

Introduction: Nasopharyngeal carcinoma (NPC) is a distinct malignancy of the head and neck with high prevalence in endemic regions and a strong association with Epstein–Barr virus (EBV). In locally advanced stages, neoadjuvant chemotherapy (NAC) followed by chemoradiotherapy improves outcomes, but response rates vary. Identifying early predictors of NAC response is essential for guiding personalized treatment strategies. This study aims to assess whether baseline [¹⁸F]FDG PET/CT parameters can predict NAC response in NPC patients. Methods: In this retrospective study, 27 patients with histologically confirmed, locally advanced (stage III) NPC underwent baseline [¹⁸F]FDG PET/CT prior to NAC between 2015 and 2023. Quantitative PET parameters including SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were extracted from the primary tumor. NAC response was assessed using RECIST 1.1 criteria and classified as responders (CR + PR) or non-responders (SD + PD). Group comparisons were performed using Student’s t-test. ROC analysis was used to identify optimal cut-off values. A p-value < 0.05 was considered significant. Results: The cohort included 20 males and 7 females (mean age: 60.8 ± 15.2 years). The predominant histotype was undifferentiated non-keratinizing carcinoma (92.6%). A total of 19 patients (70.4%) responded to NAC. Responders had significantly lower baseline SUVmax (10.9 ± 4.8 vs. 15.8 ± 4.1, p = 0.021), MTV (16.2 ± 12.4 vs. 27.8 ± 19.5 cm³, p = 0.045), and TLG (128.6 ± 98.2 vs. 218.7 ± 152.4, p = 0.038). SUVmean was also lower in responders (6.1 ± 2.1 vs. 9.3 ± 2.8), although not statistically reported. ROC analysis identified SUVmax > 12.5 and MTV > 20.0 cm³ as thresholds associated with poor NAC response. Conclusions: Baseline metabolic parameters from [¹⁸F]FDG PET/CT, particularly SUVmax and MTV, may assist stratification of NAC response in nasopharyngeal carcinoma. These biomarkers may facilitate pre-treatment stratification and guide more personalized therapeutic approaches. However, the limited sample size may affect the generalizability of these findings, and larger prospective studies are needed to confirm the results. Full article

Purpose: This study aims to determine whether body composition parameters affect progression-free survival (PFS) in patients with hormone receptor positive and HER-2 negative metastatic breast cancer treated with ribociclib as first-line therapy. Materials and methods: It was designed as a single-center, retrospective study; therefore, its generalizability is limited. At the start of treatment, ¹⁸F-FDG PET/CT scans were performed on patients, and subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volume, SAT and VAT SUV (standardized uptake value) mean, SAT and VAT index, skeletal muscle index (SMI), and skeletal muscle radiodensity (SMD) were calculated at the L3 vertebra level. The albumin-myosteatosis gauge (AMG) was defined as SMD × albumin. Results: The study included 73 participants. Increased SAT and VAT volumes were associated with worse PFS (23.4 vs. 35.5 months, p: 0.015; 25.4 vs. 33.3 months, p: 0.114). However, in the multivariable cox regression analysis for progression free survival (PFS), an increase in SAT volume [HR 4.96; p: 0.038)] and SAT SUV mean [HR 2.99; p: 0.016)] were identified as independent risk factors. Conclusions: It should be noted that in patients treated with ribociclib, increases in SAT volume and SAT SUV mean are independent risk factors for PFS. Full article

Background/Objectives: Sarcoidosis is a systemic inflammatory disease that can cause cardiac autonomic dysfunction (SCAD), often underrecognized despite its clinical importance. While [¹⁸F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ([¹⁸F]FDG PET/CT) and cardiac magnetic resonance imaging (CMR) assess cardiac involvement, [¹²³I]-meta-iodinebenzylguanidine ([¹²³I]MIBG) scintigraphy evaluates cardiac sympathetic innervation, offering complementary insights to potentially improve SCAD detection and management. This retrospective study explores the role of [¹²³I] MIBG scintigraphy in detecting SCAD among patients with unexplained cardiac symptoms. It focuses on its potential to provide complementary diagnostic information in patients where established imaging techniques, such as [¹⁸F]FDG PET/CT and CMR, fail to detect cardiac sarcoidosis. Methods: Sarcoidosis patients referred to the St. Antonius Hospital (2017–2024) who underwent [¹²³I]MIBG scintigraphy were included. Collected data encompassed demographics, SCAD symptoms, cardiac imaging findings, and carvedilol treatment outcomes. [¹²³I] MIBG abnormalities were defined as a heart-to-mediastinal ratio ≤1.6 or a washout rate ≥20%. Results: Among the final cohort of 40 sarcoidosis patients with unexplained cardiac symptoms and normal [¹⁸F]FDG PET/CT and CMR findings, 19 patients (48%) showed abnormal [¹²³I] MIBG scintigraphy results suggestive of SCAD. No significant differences were observed in clinical characteristics between patients with normal and abnormal [¹²³I]MIBG findings. Of the 16 patients treated with carvedilol, 88% reported symptom improvement, although 50% experienced side effects. Conclusions: [¹²³I]MIBG scintigraphy revealed abnormalities in a substantial number of sarcoidosis patients with unexplained cardiac symptoms despite normal [¹⁸F]FDG PET/CT and CMR. These findings indicate a potential role for [¹²³I]MIBG in detecting SCAD, but prospective studies are needed to confirm their clinical significance. Full article

Background: Malignant melanoma remains an oncological challenge, with advanced-stage five-year survival rates under 20%. Precise molecular imaging has become indispensable for accurate staging, selection of targeted or immunotherapies, treatment response assessment, and early detection of immune-related adverse events. This review examines the roles of PET/CT, PET/MRI, and SPECT/CT radiopharmaceuticals in melanoma management and highlights novel tracers and theranostic strategies poised to enhance precision nuclear medicine in this disease. Methods: We performed a review of English-language literature from January 2000 through June 2025, querying PubMed, Scopus, and clinical-trial registries for original research articles, meta-analyses, clinical guidelines, and illustrative case reports. Eligible studies investigated PET/CT, PET/MRI, or SPECT/CT applications in melanoma diagnosis, nodal and distant staging, therapy monitoring, irAE (immune-related adverse events) detection, and the development of emerging radiotracers or theranostic radiopharmaceutical pairs. Results:¹⁸F-FDG PET/CT demonstrated a high detection rate for distant metastases, outperforming conventional CT and MRI in advanced disease, despite limited resolution for infracentimetric nodal deposits. PET/MRI offers comparable diagnostic accuracy with superior soft-tissue contrast and improved brain lesion detection, while SPECT/CT enhanced sentinel lymph node localization prior to surgical biopsy. Also, FDG PET/CT identified visceral irAEs with great sensitivities, revealing asymptomatic toxicities in up to one-third of patients. Emerging radiotracers targeting melanin, fibroblast activation protein, PD-1 (programmed cell death protein 1)/PD-L1 (programmed cell death-ligand 1), and CD8⁺ T cells have demonstrated enhanced tumor specificity and are on their way to forming novel theranostic pairs. Conclusions: While ¹⁸F-FDG PET/CT remains the cornerstone of melanoma imaging, complementary advantages of PET/MRI and SPECT/CT imaging refine melanoma management. The advent of highly specific radiotracers and integrated theranostic approaches heralds a new era of tailored nuclear-medicine strategies, promising improved patient stratification, therapy guidance, and clinical outcomes in melanoma. Full article

Neuroendocrine tumors of unknown primary (CUP-NET) present a diagnostic challenge when conventional imaging fails to localize the primary tumor. This study aimed to evaluate the diagnostic value of concurrent [⁶⁸Ga]Ga-DOTA-TOC and [¹⁸F]FDG PET/CT imaging in localizing primary tumors in patients with histologically confirmed CUP-NET. Thirty-four patients underwent both imaging modalities as part of a prospective imaging protocol after negative conventional imaging or [¹¹¹In]In-octreotide scintigraphy. Primary tumor detection rates were assessed, and imaging characteristics compared between the two modalities. The overall localization rate was 58.9% (20/34). Of these, 90% (18/20) of primary tumors were identified solely by [⁶⁸Ga]Ga-DOTA-TOC PET/CT, with the remaining two visualized by both modalities. [¹⁸F]FDG PET/CT did not independently localize any primary tumors. Identified primaries were limited to grade 1 (60%) or grade 2 (40%) tumors, predominantly in the small intestine (95%). Among localized cases, 45% (9/20) underwent surgical resection and 15% (3/20) became eligible for peptide receptor radionuclide therapy. [⁶⁸Ga]Ga-DOTA-TOC PET/CT demonstrated superior detection of metastatic lesions compared to [¹⁸F]FDG PET/CT (97.1% vs. 70.6%, p = 0.006). No significant survival differences were observed between patients with localized versus non-localized primaries. These findings support the value of [⁶⁸Ga]Ga-DOTA-TOC PET/CT for identifying primary tumors in CUP-NET. Further research is warranted to explore the role of [¹⁸F]FDG PET/CT in high-grade NETs. Full article