To date, there are no clear recommendations for the treatment of a clinically inconspicuous neck (cN0) in sinonasal squamous cell carcinoma. Elective neck dissection or neck irradiation appears too aggressive given the relatively low occult metastasis rates. However, the development of neck lymph node metastases is significantly associated with worse survival, therefore patients at relevant risk need to be identified. The aim of this trial was to evaluate feasibility and safety of sentinel node biopsy for sinonasal squamous cell carcinoma. This was a prospective, single-arm, open label, multicentric pilot trial (phase II) designed to evaluate the safety and feasibility of sentinel node biopsy (SNB) of patients with sinonasal squamous cell carcinoma and clinical N0 status. 24 h before surgery, radiocolloids were injected around the tumor and lymphoscintigraphy with single-photon emission computed tomography (SPECT)/computed tomography (CT) was performed. After resection of the primary tumor, the sentinel lymph node was identified using a gamma probe and resected via minimal invasive incision. At least one sentinel node could be detected in each of the 22 patients, predominantly in level Ib and IIa. The average lymph node yield after SNB was two, and 122.7
Alveolar echinococcosis (AE) is a rare, potentially fatal zoonosis with highly heterogeneous morphology. This study compares AE lesions in B-scan ultrasound, categorized according to the Echinococcus multilocularis Ulm Classification – Ultrasound (EMUC-US), with the maximum standardized uptake value (SUVmax) in 18F-Fluorodeoxyglucose Positron-Emission-Tomography (18F-FDG-PET/CT). 18F-FDG-PET/CT is the gold standard for evaluating disease activity, with SUVmax as the key parameter indirectly reflecting AE lesion activity. Retrospective analysis of data from the German National Echinococcosis Database. A total of 121 patients with 18F-FDG-PET/CT and B-scan ultrasound (US) between 2018–2019 were included. Based on EMUC-US, AE liver lesions were compared with the corresponding SUVmax in PET/CT. Additionally, SUV ratios (SUVTLR=tumor SUVmax/liver SUVmean) were calculated. The mean SUVmax, regardless of the EMUC-US subtype, was 6.0 ± 3.3 (range: 2.4–18.0). SUVmax comparison between subtypes shows significant differences (p<0.001). The highest SUVmax and SUVTLR were measured for the pseudocystic pattern with a mean of 9.2 ± 3.5 (range: 4.1–18.0). In contrast, the metastasis-like pattern yielded 3.7 ± 0.9 (range: 2.4–5.8) and the lowest SUVTLR. An SUVmax of 6.1 ± 3.3 (range: 2.6–16.8) was measured for the hailstorm pattern and 5.8 ± 2.2 (range: 3.6–10.4) for the hemangioma-like pattern. The results show significant differences between specific US patterns and the corresponding SUVmax. Lesions with very high or low SUV correlate with characteristic morphological patterns. Hence, in clinical practice B-scan can be a valuable bedside tool for assessing certain lesions. For evaluating inflammatory activity, 18F-FDG-PET/CT remains the method of choice.
Background:Alveolar echinococcosis (AE) is a rare but potentially life-threatening parasitic disease caused by the larval stage of Echinococcus multilocularis, primarily affecting the liver with infiltrative, tumor-like growth. Sectional imaging plays a pivotal role in diagnosis, staging, and treatment planning. This study aimed to systematically evaluate the initial imaging findings in a cohort of patients with suspected AE, focusing on morphological and metabolic imaging features and their implications for staging and therapeutic decision-making. Methods:We retrospectively analyzed all patients who presented with suspected AE at the University Hospital Ulm between January 2019 and December 2023 and had F-18-fluorodeoxyglucose positron emission tomography (F-18-FDG-PET/computed tomography [CT] or PET/ magnetic resonance imaging [MRI]) and/or MRI within 6 months of presentation. PET imaging was visually assessed for increased FDG uptake as a marker of metabolic activity. Lesions were classified according to the Kodama MRI classification. Imaging-based staging was performed using the PNM classification and compared with the clinical PNM stage. Results:A total of 203 patients were included. PET imaging was performed in 198 cases (97.5%), while MRI was available in 94 patients (46.3%). Kodama types 2 (n = 30) and 3 (n = 55) were the most frequent lesion types. In the subgroup with both PET and MRI imaging (n = 89), PET activity was observed in 96.4% of Kodama type 2 and 90.6% of type 3 lesions, while no FDG uptake was noted in type 5 lesions. Imaging-based PNM classification disagreed with clinical staging in 56 cases (27.6%), likely due to standardized review by experienced radiologists and nuclear medicine specialists. PET/CT proved valuable for assessing extrahepatic and distant involvement, offering a whole-body evaluation that was more consistent than MRI, which often varied in protocol and anatomical coverage. Conclusion:F-18-FDG-PET/CT is a cornerstone in the initial diagnostic workup and staging of AE, enabling both assessment of disease extent and evaluation of inflammatory activity in specialized centers. While MRI provides essential morphological details, its limited availability and heterogeneous acquisition protocols reduce its utility for comprehensive staging. Kodama lesion types correlate with metabolic activity, but further studies are needed to clarify their prognostic relevance. Our findings underscore the importance of standardized imaging protocols and the central role of PET/CT in managing newly diagnosed AE.
Background: Alveolar echinococcosis (AE) is a severe larval tapeworm infection with a variable clinical course of the disease. Reliable imaging techniques and biomarkers are needed to predict the course of the disease. Methods: 179 AE patients that received PET/CT scans between 2008 and 2012 were retrospectively included. From stored blood samples taken on the day of the scan, levels of IgE, parasite-specific serology, amyloid A, C-reactive protein, soluble interleukin 2 receptor, cytokeratin fragments, eosinophilic cell count, and eosinophil cationic protein were measured. Additionally, the current clinical outcome (cured, stable, or progressive disease) after a median duration of 8 years after baseline examination was assessed. Ultimately, an ordinal logistic regression was conducted to evaluate which imaging parameters and biomarkers independently influence the clinical outcome. Results: In general, patients in need of medical treatment or with progressive disease, advanced PNM stages, and positive PET/CT scans exhibited higher levels of the respective biomarkers. However, only the parasite-specific serological markers and total IgE levels differed significantly between clinical groups, WHO PNM stages, and the results of the PET/CT scan. In the multivariate analysis, PET/CT results were a strong predictor of the clinical outcome (OR 8.908, 95%CI 3.019–26.285; p < 0.001), and age at baseline was a moderate predictor (OR 1.031, 95%CI 1.003–1.060; p = 0.029). Conclusions: The PET/CT scan is, preferably in combination with parasite-specific serology and IgE levels, a valuable tool in the clinical management of AE and is able to predict the course of the disease.
Recent improvements in alveolar echinococcosis (AE) therapy can provide long-term disease control, and even allow structured treatment interruption in selected cases. Imaging has a pivotal role in monitoring disease activity, with 18-fluoro-deoxyglucose positron emission and computed tomography (18F-FDG-PET/CT) in particular having proven beneficial for assessing disease activity. Repetitive regular examinations to monitor therapy response, however, can lead to substantial radiation burden. Therefore, by combining metabolic information and excellent tissue contrast in magnetic resonance imaging (MRI), PET/MR appears ideally suited for this task. Here, we retrospectively analyzed 51 AE patients that underwent 18F-FDG-PET/MR. Patients had a ‘confirmed/probable’ diagnosis in 22/29 cases according to the WHO classification. FDG uptake, diffusion restriction, and MRI morphology were evaluated. We found significant differences in FDG uptake between responders to benzimidazole therapy and progressive manifestations (SUVavg 2.7 ± 1.3 vs. 5.4 ± 2.2, p < 0.001) as well as between Kodama Types 1 and 3 (F = 9.9, p < 0.003). No significant differences were detected for ADC values or MRI morphology concerning response and no correlations were present between FDG uptake and ADC values. The mean radiation dose was 5.9–6.5 mSv. We conclude that the combination of metabolic information and MRI morphology at a low radiation dose proposes PET/MR as a suitable imaging modality for AE assessment. Longitudinal studies are needed to define the role of this imaging modality.
Nanodiamonds (NDs) have high potential as a drug carrier and in combination with nitrogen vacancies (NV centers) for highly sensitive MR-imaging after hyperpolarization. However, little remains known about their physiological properties in vivo. PET imaging allows further evaluation due to its quantitative properties and high sensitivity. Thus, we aimed to create a preclinical platform for PET and MR evaluation of surface-modified NDs by radiolabeling with both short- and long-lived radiotracers. Serum albumin coated NDs, functionalized with PEG groups and the chelator deferoxamine, were labeled either with zirconium-89 or gallium-68. Their biodistribution was assessed in two different mouse strains. PET scans were performed at various time points up to 7 d after i.v. injection. Anatomical correlation was provided by additional MRI in a subset of animals. PET results were validated by ex vivo quantification of the excised organs using a gamma counter. Radiolabeled NDs accumulated rapidly in the liver and spleen with a slight increase over time, while rapid washout from the blood pool was observed. Significant differences between the investigated radionuclides were only observed for the spleen (1 h). In summary, we successfully created a preclinical PET and MR imaging platform for the evaluation of the biodistribution of NDs over different time scales.
Aim Recently, dose reference levels (DRLs) have been defined in Germany for auxiliary low-dose CT scans in hybrid SPECT/CT and PET/CT examinations, based on data from 2016/17. Here, another survey from 2020 was evaluated and compared with the new DRLs as well as with similar surveys from foreign countries. Methods The survey, which had already been conducted in the Nordic countries, queried for various examinations including the following values: patient weight and height, volume CT dose index (CTDI (vol) ), dose length product (DLP). For each examination, statistical parameters such as the third quartile (Q3) were determined from all submitted CTDI (vol) and DLP values. Additionally, for examinations comprising datasets from at least 10 systems, the third quartile (Q3-Med) of the respective median values of each system was calculated. Q3 and Q3-Med were compared with the newly published DRLs from Germany and values from similar studies from other countries. Results Data from 15 SPECT/CT and 13 PET/CT systems from 15 nuclear medicine departments were collected. For the following examinations datasets from more than 10 systems were submitted: SPECT lung VQ, SPECT bone, SPECT&PET cardiac, PET brain, PET oncology. Especially for examinations of the thorax and heart, the new DRLs are very strict compared to this study. The CTDI (vol) values for examinations of the head were lower in this study than the DRLs prescribe now. Conclusions For certain examination types, there is a need for dose optimization at some clinics and devices in order to take into account the new DRLs in Germany in the future.
Human alveolar echinococcosis (AE), which is caused by the cestode Echinococcus (E.) multilocularis, is an epidemiologically relevant issue in modern medicine and still poses a diagnostic and therapeutic challenge. Since diagnosis mainly relies on imaging procedures and serological testing, we retrospectively and comparatively analyzed the performance of an Echinococcus IgG screening ELISA, whole serum IgE, and two specific confirmatory ELISA platforms using the defined E. multilocularis antigens Em2-Em18 (Em2+) and recombinant Em18 (recEm18). With special emphasis on the clinical usefulness of recEm18, we correlated the laboratory results with clinical characteristics and imaging findings in a large and well-characterized cohort of N = 124 AE patients, who were followed over several years after either surgical plus subsequent pharmacological treatment or pharmacotherapy alone. All patients had routinely received PET-CTI every two years. Our data reveal strong correlations for both Echinococcus IgG and recEm18 with tracer uptake in PET-CTI and parasitic lesion size and number, suggesting additional clinical usefulness of recEm18 for certain constellations only, while IgG and Em2+ still appear reasonable and sensitive screening methods for initial diagnosis of AE. With this study, we aim to contribute to further optimizing medical care of AE patients. For instance, it might be reasonable to consider the replacement of some PET-CTI follow-ups by imaging procedures with less radiation exposure or serological means alone. Further studies that clarify the correlation of serological markers with ultrasound criteria might be particularly useful, and further retrospective as well as prospective investigations are justified in this context.
Zusammenfassung Die PSMA-PET/CT hat durch die präzise Darstellung der Tumorausdehnung einen festen Stellenwert in der Diagnostik, insbesondere in der Rezidivsituation, eingenommen und ist bereits in mehreren nationalen und internationalen Leitlinien fest verankert. Sie ermöglicht, in einem Untersuchungsgang Informationen über die Tumorsituation in der Prostataloge und von potenziellen lymphonodalen, viszeralen und ossären Metastasen zu erlangen, die für die zunehmend personalisierten Behandlungsstrategien notwendig sind. Die PSMA-Therapie stellt bereits jetzt – trotz bisher fehlender Zulassung – eine ergänzende nebenwirkungsarme Therapie beim metastasierten kastrationsresistenten Prostatakarzinom dar, die die Lebensqualität der Patienten deutlich verbessern und die Überlebenszeit steigern kann ohne relevante Toxizität, und deren Potenzial für die Zukunft auch durch Kombination mit anderen Therapieverfahren noch lange nicht absehbar ist. Der Beitrag thematisiert die Einsatzgebiete der PSMA-PET-Bildgebung als Grundlage für die erfolgreiche Therapie sowie den aktuellen Stand zur Indikation, Durchführung und Entwicklung der PSMA-Therapie.
Tumor or target heterogeneity (TH) implies presence of variable cellular populations having different genomic characteristics within the same tumor, or in different tumor sites of the same patient. The challenge is to identify this heterogeneity, as it has emerged as the most common cause of 'treatment resistance', to current therapeutic agents. We have focused our discussion on 'Prostate Cancer' and 'Neuroendocrine Tumors', and looked at the established methods for demonstrating heterogeneity, each with its advantages and drawbacks. Also, the available theranostic radiotracers targeting PSMA and somatostatin receptors combined with targeted systemic agents, have been described. Lu-177 labeled PSMA and DOTATATE are the 'standard of care' radionuclide therapeutic tracers for management of progressive treatment-resistant prostate cancer and NET. These approved therapies have shown reasonable benefit in treatment outcome, with improvement in quality of life parameters. Various biomarkers and predictors of response to radionuclide therapies targeting TH which are currently available and those which can be explored have been elaborated in details. Imaging-based features using artificial intelligence (AI) need to be developed to further predict the presence of TH. Also, novel theranostic tools binding to newer targets on surface of cancer cell should be explored to overcome the treatment resistance to current treatment regimens.
Chronic total occlusion (CTO) of coronary arteries is a common finding in patients with known or suspected coronary artery disease (CAD). Although tremendous advances have been made in the interventional treatment of CTOs over the past decade, correct patient selection remains an important parameter for achieving optimal results. Non-invasive imaging can make a valuable contribution. Ischemia and viability, two major factors in this regard, can be displayed using echocardiography, single-photon emission tomography, positron emission tomography, computed tomography, and cardiac magnetic resonance imaging. Each has its own strengths and weaknesses. Although most have been studied in patients with CAD in general, there is an increasing number of studies with positive preselectional factors for patients with CTOs. The aim of this review is to provide a structured overview of the current state of pre-interventional imaging for CTOs.
Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disorder affecting children and adolescents. Previously classified as a rare disease, recent studies suggest a higher incidence of the disease. CNO may develop into the clinical presentation of chronic recurrent osteomyelitis (CRMO) with high relapse rate and multifocality. Diagnosis of CNO/CRMO is often delayed, with implications for disease severity and relapse rate. This can be significantly improved by knowledge of the disease entity and its characteristics. Imaging plays a key role in diagnosis, differential diagnosis and therapy monitoring. Magnetic resonance imaging (MRI) has several advantages compared to other imaging methods and is increasingly applied in clinical studies. Recent studies show that a whole-body (WB) coverage (WB-MRI) without contrast agent administration is a rational approach. This educational review is based on a systematic analysis of international peer-reviewed articles and presents our own clinical experiences. It provides an overview of disease entity, incidence and clinical diagnosis. The role of imaging, especially of whole-body MRI, is discussed in detail. Finally, practical advice for imaging, including flowcharts explaining when and how to apply imaging, is provided. Knowing the specifics of CNO/CRMO and the importance of MRI/whole-body MRI allows rapid and efficient diagnosis as well as therapy support and helps to avoid irreversible secondary damage.
Whooping cough is caused by Bordetella pertussis that releases pertussis toxin (PT) which comprises enzyme A-subunit PTS1 and binding/transport B-subunit. After receptor-mediated endocytosis, PT reaches the endoplasmic reticulum from where unfolded PTS1 is transported to the cytosol. PTS1 ADP-ribosylates G-protein α-subunits resulting in increased cAMP signaling. Here, a role of target cell chaperones Hsp90, Hsp70, cyclophilins and FK506-binding proteins for cytosolic PTS1-uptake is demonstrated. PTS1 specifically and directly interacts with chaperones in vitro and in cells. Specific pharmacological chaperone inhibition protects CHO-K1, human primary airway basal cells and a fully differentiated airway epithelium from PT-intoxication by reducing intracellular PTS1-amounts without affecting cell binding or enzyme activity. PT is internalized by human airway epithelium secretory but not ciliated cells and leads to increase of apical surface liquid. Cyclophilin-inhibitors reduced leukocytosis in infant mouse model of pertussis, indicating their promising potential for developing novel therapeutic strategies against whooping cough.
1246 Aim: Nanoparticles (NP) are of particular interest for medical applications due to their high biocompatibility and highly adaptable surface. The biodistribution and biostability of the particles is usually studied in animal experiments with rodents. The Hen9s Egg Test-Chorioallantoic Membrane (HET-CAM) in vivo model is a good alternative to animal experiments with regard to the 3R principles of animal welfare and has already been successfully used for peptide studies. The suitability of the model for biodistribution studies of particles is analyzed in this project. Therefore, nanodiamonds (ND), mesoporous silica (MSN) and superparamagnetic iron oxide NP (SPION) were studied with respect to biodistribution in the HET-CAM model. Methods: ND coated with deferoxamine (DFO) coupled with human serum albumin, SPION modified with PEG (polyethylene glycol), and MSN functionalized with a fragment of CD47 protein and DFO were examined. All particles were radiolabeled using 89Zr. The stability of the labeling was monitored in 0.9% NaCl, cell culture medium, and human serum over an observation period of five days. After i.v. injection, PET (Focus 120 Siemens Medical Solutions, Inc., Erlangen, Germany) and/or MRI (BioSpec 117/16, Bruker, Ettlingen, Germany) measurements were performed depending on the particle specificity. All measurements were performed between embryo development day 12 and 16. Results: 89Zr-radiolabeling yields of >76% were achieved for all NP. The stability of the labeling ranged from 77% (SPION) to 99% (MSN). An accumulation of MSN (6.5 ± 1.7) %IA/cc (n=3) and ND (10.0 ± 5.3) %IA/cc (n=4) was observed in the liver by overlaying PET and MRI data. In T1-weighted MR images, SPION caused signal reduction in the liver. The ratios of the corresponding signal intensities of liver-to-chest muscle (n=3) were 2.7 ± 0.2 before and 10.2 ± 1.2 (0h) to 9.6 ± 3.7 (4h) after injection. Conclusions: The assessment of the biodistribution of various radiolabeled NP using high-resolution MR and PET imaging was successfully demonstrated. The particles accumulated in the liver of the chick embryo, similar to the distribution in mice, suggesting poor blood retention and the need to improve the surface modification. Despite model-related limitations, the HET-CAM model could help to reduce the number of animal experiments required, especially in the early stages of compound development.
Volker Rasche合作论文数Philips Medical Systems2