Search Results (289)

Alzheimer’s disease (AD) is a progressive neurodegenerative condition representing the most common cause of dementia and currently affects millions of people worldwide. The clinical presentation includes memory impairment, cognitive decline, and neuropsychiatric symptoms, reflecting pathological hallmarks such as β-amyloid (Aβ) plaques, neurofibrillary tangles, synaptic dysfunction, and neuroinflammation. Despite being the gold standard for detecting amyloid and tau pathologies in vivo, cerebrospinal fluid (CSF) biomarkers and positron emission tomography (PET) imaging are not widely used in the clinical setting because of invasiveness, high costs, and restricted accessibility. Recent advances in blood-based biomarkers offer a promising and minimally invasive tool for early detection, diagnosis, and monitoring of AD. Ultra-sensitive analytical platforms, including single-molecule arrays (Simoa) and immunoprecipitation-mass spectrometry, now enable reliable quantification of plasma Aβ isoforms, phosphorylated tau variants (p-Tau181, p-Tau217, p-Tau231), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). In addition, blood biomarkers reflecting oxidative stress, neuroinflammation, synaptic disruption and metabolic dysfunction are under active investigation. This narrative review synthesizes current evidence on blood-based biomarkers in AD, emphasizing their biological relevance, diagnostic accuracy, and clinical applications. Finally, we highlight forthcoming challenges, such as standardization, and future directions, including the use of artificial intelligence in precision medicine. Full article

Background/Objectives: This study evaluated a novel PET tracer, ⁶⁸Ga-NOTA-CYT-200, which targets human granzyme B (GZB) as a biomarker for cytotoxic T-cell activation in a clinically relevant model of melanoma-bearing mice with a humanized immune system treated with immune checkpoint inhibitor (ICI) therapy. Methods: The binding affinity of the tracer was determined using an enzymatic colorimetric assay. Tumor-bearing humanized NSG mice underwent PET imaging before and during ICI monotherapy or combination therapy to assess ⁶⁸Ga-NOTA-CYT-200 uptake within tumors and other organs. The tumor growth was carefully monitored. The treatment response was evaluated based on the percentage change in tumor size at days 5 and 15 after the treatment started. A tracer biodistribution study and immunohistochemical staining of the tumors and organs were also performed. Results: The inhibition constant (Ki) of ⁶⁸Ga-NOTA-CYT-200 was estimated at 4.2 nM. PET imaging showed a significantly higher ⁶⁸Ga-NOTA-CYT-200 uptake in mice receiving the combination therapy compared to those receiving monotherapy or a vehicle (p < 0.0001 or p = 0.0005, respectively), which correlated with the greatest reduction in tumor size in the combination ICI group. Regardless of treatment, the responders presented with a significantly higher ⁶⁸Ga-NOTA-CYT-200 uptake at days 4 or 7 after the treatment began (p = 0.0002 and p = 0.0109, respectively). An increased uptake of ⁶⁸Ga-NOTA-CYT-200, especially in the intestines and liver within the combination ICI group, suggested immune-related adverse events (IrAEs). Conclusions: Our study demonstrates that ⁶⁸Ga-NOTA-CYT-200 PET imaging can predict the early treatment response in melanoma models treated with ICI and may also help in detecting IrAEs. Full article

Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer is the most prevalent subtype. Positron emission tomography (PET) imaging with 16α-18F-fluoro-17β-fluoroestradiol (¹⁸F-FES), a radiolabeled form of estradiol, enables the assessment in vivo of ER expression, ER heterogeneity in metastatic sites and functionally active ER capable of ligand binding. This imaging modality has been recently approved as a diagnostic tool for detecting ER-positive lesions in patients with recurrent or metastatic breast cancer. Despite promising activity, the role of this powerful tool is still debated. Herein we critically analyzed current evidence supporting the use of 18F-FES PET in metastatic ER+/HER2− breast cancer, highlighting the potential challenges for clinical implementation. Full article

Immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) have revolutionized cancer therapy, substantially improving survival across a broad range of malignancies. However, these agents are associated with a unique profile of endocrine immune-related adverse events (irAEs), including thyroiditis, hypophysitis, adrenalitis, and pancreatitis, which differ significantly from the toxicities seen with conventional chemotherapy. These complications often arise unpredictably during treatment and may result in irreversible hormone deficiencies requiring lifelong replacement, underscoring the importance of early detection. ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) has emerged as a valuable tool not only for oncologic staging and response assessment but also for detecting metabolic changes in endocrine organs. PET/CT can identify irAEs before the appearance of clinical symptoms or biochemical abnormalities. Emerging evidence suggests that the presence of endocrine irAEs identified by ¹⁸F-FDG PET/CT may correlate with improved treatment response and survival, possibly reflecting enhanced immune activation. This comprehensive review discusses the role of ¹⁸F-FDG PET/CT in the early recognition of therapy-induced endocrine toxicities, facilitating timely intervention through hormone replacement or immunosuppressive therapy while minimizing unnecessary treatment interruptions. Effective integration of metabolic imaging with clinical and laboratory evaluation requires coordinated multidisciplinary collaboration among oncologists, endocrinologists, and nuclear medicine physicians to optimize outcomes and reduce endocrine-related morbidity in the era of precision oncology. Full article

Background/Objectives: Electrochemotherapy (ECT) has emerged as a promising locoregional treatment modality for patients with cutaneous and subcutaneous melanoma metastases. While systemic therapies have improved overall disease control, effective local tumor management remains crucial, particularly in oligometastatic or symptomatic disease. This pilot study investigates the role of metabolic imaging with [¹⁸F]FDG PET/CT to assess tumor metabolism in melanoma patients undergoing ECT, building on prior evidence that PET offers valuable functional information beyond anatomical changes detected by conventional imaging. Methods: This retrospective study included 11 patients with histologically confirmed melanoma and cutaneous or subcutaneous metastases treated with ECT. [¹⁸F]FDG PET/CT scans were performed either before ECT, after ECT, or both. Metabolic response was assessed by measuring the tracer uptake (SUV_max) of the ten hottest lesions. Morphological changes were evaluated using CT. Local progression-free survival was determined. Results: A total of 66 lesions were analyzed. Patients with PET/CT only after ECT showed significantly higher SUV_max and lesion size compared to those imaged before treatment (mean SUV_max: 9.9 ± 11.2 vs. 10.3 ± 5.5; p = 0.034). Progression-free survival differed significantly based on pre-ECT SUV_max values (χ² = 3.90; p = 0.048). Among two patients with follow-up imaging, one showed new lesions on CT with only mild FDG uptake, while the other developed newly FDG-avid metastases after ECT. Conclusions: FDG PET/CT provides valuable information on tumor viability and treatment response in melanoma patients undergoing ECT, demonstrated by significant differences in metabolic activity between lesions imaged before and after treatment. The lack of longitudinal intra-individual imaging limits definitive conclusions about the direct metabolic effects of ECT. Full article

Background/Objectives: ¹⁸F-PSMA-1007 is one of the more widely used radioligands in prostate cancer imaging with PET/CT. Its major advantage lies in the low urinary tracer activity due to primarily hepatobiliary clearance, but unexpectedly high tracer accumulation in the bladder can occur, potentially hindering assessment of lesions near the prostate bed. This study assesses the impact of furosemide on ¹⁸F-PSMA-1007 tracer accumulation in the bladder. Methods: In this single-center, retrospective, intra-individual comparative analysis, 18 patients undergoing two consecutive ¹⁸F-PSMA-1007 PET/CT scans for biochemical relapse (BCR) or persistence (BCP)—one with and one without prior furosemide administration—were included. Images were acquired 60 min post-injection of 250 MBq of tracer activity. Standardized Uptake Values (SUVmax, SUVpeak, SUVmean) were measured in the bladder and in tissues with physiological uptake by three readers. Differences were analyzed using Wilcoxon signed-rank tests. The inter-reader agreement was assessed using intraclass correlation coefficient. Results: Furosemide significantly decreased bladder SUVmax, SUVpeak, and SUVmean (all p < 0.001). Mean bladder SUVmax decreased from 13.20 ± 10.40 to 3.92 ± 3.47, SUVpeak from 10.94 ± 8.02 to 3.47 ± 3.13, and SUVmean from 8.74 ± 6.66 to 2.81 ± 2.56, representing a large effect size (r ≈ 0.55). Physiological tracer uptake in most organs was not significantly influenced by furosemide (all p > 0.05). Conclusions: Despite the predominantly hepatobiliary clearance of ¹⁸F-PSMA-1007, furosemide-induced forced diuresis leads to a significant reduction in tracer activity in the bladder, which in clinical practice could help in early detection of tumor recurrence. Full article

Positron emission tomography (PET) and liquid biopsy have independently transformed prostate cancer management. This review explores the complementary roles of PET imaging and liquid biopsy in prostate cancer, focusing on their combined diagnostic, monitoring, and prognostic potential. A systematic search of PubMed, Scopus, and Cochrane Library databases was conducted to identify human studies published in English up to January 2025. Seventeen studies met the inclusion criteria and were analyzed according to PRISMA guidelines. Across the included studies, PET-derived imaging metrics, such as metabolic activity and radiotracer uptake, correlated consistently with liquid biopsy biomarkers, including circulating tumor cells and cell-free DNA. Their joint application demonstrated added value in early detection, treatment monitoring, and outcome prediction, particularly in castration-resistant prostate cancer. Independent and synergistic prognostic value was noted for both modalities, including survival outcomes such as overall survival and progression-free survival. Combining PET imaging and liquid biopsy emerges as a promising, non-invasive strategy for improving prostate cancer diagnosis, monitoring, and therapeutic stratification. While preliminary findings are encouraging, large-scale prospective studies are essential to validate their integrated clinical utility. Full article

Infections caused by oxacillin-resistant Staphylococcus pseudintermedius are increasingly common in veterinary medicine. The indiscriminate use of antibiotics by pet owners worsens this problem, reducing treatment efficacy and creating the need for alternative therapies. This study aimed to evaluate the inhibitory effect of clove essential oil (Syzygium aromaticum) on both oxacillin-resistant and susceptible S. pseudintermedius. Thirty-five isolates from dogs with otitis externa were analyzed. The bacteria were identified by phenotypic tests and tested for susceptibility to 22 antibiotics using disk diffusion. Resistance genes (mecA and blaZ) were detected using conventional PCR. Among the isolates, 34.28% (12/35) were positive for mecA, and 97.14% (34/35) for blaZ. The essential oil’s efficacy was assessed using broth microdilution to determine its minimum inhibitory concentration (MIC). Clove oil showed an average MIC and minimum bactericidal concentration (MBC) of 6.4 mg/mL, inhibiting both resistant and susceptible isolates. In conclusion, clove essential oil demonstrated in vitro antimicrobial activity against S. pseudintermedius. Full article

This study assesses the clinical deployment of SubtlePET™, a commercial AI-based denoising algorithm, across three radiotracers—¹⁸F-FDG, ⁶⁸Ga-PSMA-11, and ¹⁸F-FDOPA—with the goal of improving image quality while reducing injected activity, technologist radiation exposure, and scan time. A retrospective analysis on a digital PET/CT system showed that SubtlePET™ enabled dose reductions exceeding 33% and time savings of over 25%. AI-enhanced images were rated interpretable in 100% of cases versus 65% for standard low-dose reconstructions. Notably, 85% of AI-enhanced scans received the maximum Likert quality score (5/5), indicating excellent diagnostic confidence and noise suppression, compared to only 50% with conventional reconstruction. The quantitative image quality improved significantly across all tracers, with SNR and CNR gains of 50–70%. Radiotracer dose reductions were particularly substantial in low-BMI patients (up to 41% for FDG), and the technologist exposure decreased for high-exposure roles. The daily patient throughput increased by an average of 4.84 cases. These findings support the robust integration of SubtlePET™ into routine clinical PET practice, offering improved efficiency, safety, and image quality without compromising lesion detectability. Full article

Background: Uterine fibroids are the most common tumors in gynecology, detected in up to 80% of patients at various points in their lives. Uterine sarcomas account for 3% to 7% of all uterine cancers. The diagnosis of uterine fibroids is possible through ultrasonography (US), but this method has many limitations. More accurate examinations include magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. Methods: This study evaluates MRI and PET in differentiating uterine fibroids from sarcomas. MRI uses T2-weighted and diffusion-weighted imaging (DWI), while PET assesses metabolism and estrogen receptor activity using [18F] fluorodeoxyglucose (FDG) and 16α-[18F]-fluoro-17β-estradiol (FES). Results: MRI allows for the identification of uterine fibroids when they exhibit good delineation and low intensity in T2-weighted images and DWI. Uterine sarcoma is characterized by moderate to high signal intensity on T2-weighted imaging, irregular borders, high signal intensity at high DWI values, and a decreased apparent diffusion coefficient. PET imaging with FDG and FES is a useful tool in differentiating uterine fibroids from sarcomas. Uterine sarcomas exhibit greater FDG uptake than smooth muscle fibroids, although cases of similar uptake do occur. On the other hand, FES provides information about estrogen receptors (ERs). Conclusions: Future research should focus on conducting standardized imaging studies, which would facilitate the inclusion of larger patient cohorts. This, in turn, would enable the development of specific diagnostic guidelines, ultimately leading to more accurate diagnoses and reducing the difficulty of differentiating these tumors through imaging. Full article

Multiple sclerosis (MS) is a multifaceted inflammatory, demyelinating, and neurodegenerative disease typified by lesions with distinct hallmarks in the central nervous system. Dysregulation of micro-environmental factors, including extracellular matrix (ECM) remodelling and glial cell activation, has a decisive effect on lesion development and disease progression. Understanding the biological and pathological features of lesions would aid in prognosis and personalised treatment decision making. Positron emission tomography (PET) is an imaging technique that uses radio-labelled tracers to detect specific biological phenomena. Recent PET hardware developments enable high-resolution, quantitative imaging, which may allow biological characterisation of relatively small MS lesions. PET may complement MRI by offering objective, quantitative insights into lesion characteristics, including myelin density, inflammation and axonal integrity. Moreover, PET may provide information on lesion traits supporting decision making on upcoming therapeutic strategies for progressive MS, such as the availability of oligodendrocyte progenitor cells and ECM composition that affect remyelination and/or axon regeneration. This review explores the cellular and molecular ECM signatures and neuropathological processes of white matter MS lesions, discusses current and potential novel PET targets that may help characterise MS lesions in vivo, and addresses the potential of PET as a decision tool for selection and evaluation of therapeutic strategies, with a focus on remyelination. Full article

Background: Thymic carcinoids are rare neuroendocrine tumors arising in the anterior mediastinum, often diagnosed at an advanced stage due to nonspecific clinical manifestations. Their management remains challenging because of the paucity of data, rarity of occurrence, and aggressive biological behavior compared to other well-differentiated neuroendocrine neoplasms. Methods: We conducted a comprehensive review of the current literature focusing on the classification, clinical presentation, diagnostics, treatment options, prognostic factors, and emerging experimental therapies for thymic carcinoids. Emphasis was placed on integrating recent molecular and therapeutic advances into clinical practice. Results: Surgical resection remains the cornerstone of treatment for localized disease, while systemic therapies such as everolimus, somatostatin analogs, platinum-based chemotherapy, and peptide receptor radionuclide therapy (PRRT) are options for advanced cases. Novel diagnostic modalities, including NETest, 64Cu-DOTATATE PET, and 18F-FDOPA PET, offer promise in early detection and disease monitoring. Molecular insights, particularly involving MEN1, ATRX, and DAXX mutations, pave the way for individualized targeted therapies. Immunotherapy and radioimmunotherapy represent emerging, albeit still experimental, approaches. Prognosis largely depends on tumor stage, differentiation, resectability, and functional activity, with a high recurrence rate necessitating prolonged surveillance. Conclusions: Thymic carcinoids pose significant diagnostic and therapeutic challenges. Advances in molecular profiling, novel imaging techniques, and systemic therapies offer hope for improved outcomes. Given the disease rarity, continued collaboration through registries and multicenter studies is essential to refine evidence-based management strategies. Full article

Fipronil (FIP) and imidacloprid (IMID) are two of the most commonly used ectoparasiticides to control parasites in pets. Compared with those of farm animals, their environmental risks have generally been considered low because of their limited use; however, the growing pet population and evolving treatment practices make this assumption challenging. To assess these risks, water samples were collected at an animal shelter in Italy to monitor the abundance of ectoparasiticides in aquatic environments. Additionally, laboratory-based ecotoxicological assays were carried out on a range of marine non-target species across different trophic levels (algae, copepods, and mussels). In vitro toxicity tests on human epithelial cell cultures were also implemented to examine potential cytotoxic effects at the levels of human exposure detectable in a domestic setting after pet treatment. Wastewater samples from the shelter contained 0.18 µg L⁻¹ of IMID, 0.50 µg L⁻¹ of FIP, and 0.20 µg L⁻¹ of FIP-sulfone, with these concentrations remaining stable for 60 days. Chronic exposure to FIP and IMID at 30.0 µg L⁻¹ impaired the mobility of the copepods. The EC₁₀ and EC₂₀ values were determined to be 1.7 (0.06–6.59) µg L⁻¹ and 2.8 (0.436–8.51) µg L⁻¹ for FIP and 2.6 (0.80–6.33) µg L⁻¹ and 7.6 (3.12–15.8) µg L⁻¹ for IMID, respectively. FIP and IMID exposure led to lipid peroxidation in the digestive glands and gills of mussels, whereas only IMID exposure increased acetylcholinesterase activity in the digestive glands at concentrations between 0.5 and 5.0 µg L⁻¹. Additionally, both fipronil and imidacloprid triggered the production of reactive oxygen species and lipid peroxidation and decreased the viability of human keratinocyte cells in a concentration-dependent manner. These findings highlight the persistence and potential risks of FIP and IMID, stressing the need for stricter regulations and further research on chronic environmental exposure to safeguard ecosystems and public health. Full article

Background: Meta-analyses on the prevalence and significance of thyroid incidentalomas at PET (TIP) are available only about [¹⁸F]FDG. Focal TIP at [¹⁸F]FDG PET is not rare and may be malignant lesions in about one-third of cases. The aim of this study is to perform a meta-analysis on the prevalence and clinical significance of TIP using other PET radiotracers beyond [¹⁸F]FDG. Methods: A comprehensive literature search of studies about TIP was carried out using four different databases, screened until 31 December 2024. Only original articles about TIP using radiopharmaceuticals other than [¹⁸F]FDG were selected. A proportion meta-analysis on the prevalence and clinical significance of TIP was carried out on a patient-based analysis using a random-effects model. Results: 21 studies (29,409 patients) were included in the meta-analysis. PET was performed using radiolabeled somatostatin analogues (SSA) [n = 5], choline [n = 6], prostate-specific membrane antigen (PSMA) [n = 7], or fibroblast activation protein inhibitors (FAPI) [n = 3]. The uptake pattern of TIP was described as focal, diffuse, or mixed/heterogeneous. The pooled prevalence of TIP was 5.6% for SSA-PET, 6.1% for choline-PET, 4.2% for PSMA-PET, and 3.6% for FAPI-PET. The final diagnosis of TIP with a diffuse pattern was a benign condition or represented a physiological uptake. Conversely, TIP with focal or mixed/heterogeneous pattern may represent a benign condition in most cases, but even a malignant lesion in 6–10% of cases. Conclusions: As for [¹⁸F]FDG, TIP using other radiopharmaceuticals is not rare. Most of them are benign, but those with focal or heterogeneous uptake patterns may represent a malignant lesion in some cases (even if the risk of malignancy is lower compared to [¹⁸F]FDG PET), thus requiring further evaluation. Further studies are warranted to better clarify the clinical impact of TIP detection. Full article

Background/Objectives: Breast cancer (BC) is the most commonly diagnosed cancer worldwide. Estrogen receptor (ER) status is a key determinant in the diagnosis and treatment of BC. Although immunohistochemistry (IHC) is the gold standard for ER assessment, it has limitations. This umbrella review aims to evaluate the role of 16α-18F-fluoro-17β-estradiol ([¹⁸F]FES) PET/CT as a non-invasive imaging tool for assessing ER expression and its implications in BC management. Methods: A comprehensive search was conducted in PubMed/MEDLINE and Cochrane Library for systematic reviews and meta-analyses published in the last decade. Studies eligible for inclusion evaluated the diagnostic accuracy and clinical utility of [¹⁸F]FES PET/CT in BC based on a predefined research question “What is the role of fluoroestradiol ([¹⁸F]FES) PET/CT in breast cancer?”. Data extraction and quality assessment were performed independently by two reviewers using the AMSTAR-2 tool. Results: Eight systematic reviews met the inclusion criteria. [¹⁸F]FES PET/CT demonstrated high sensitivity (81–94%) and specificity (78–95%) in detecting ER-positive lesions. It provided a real-time, whole-body assessment of ER expression, outperforming IHC in detecting functional ER activity. Additionally, [¹⁸F]FES PET/CT showed promise in predicting treatment response and guiding therapy decisions, particularly in metastatic settings. Conclusions: This review highlights the clinical value of [¹⁸F]FES PET/CT in BC management, offering a non-invasive alternative for ER assessment with high diagnostic accuracy. Its integration into clinical practice may enhance personalized treatment strategies for BC patients. Full article