We report a case that combines several aspects of molecular diagnostics and clinical follow-up with innovative imaging of [89Zr]Zr-DFO-trastuzumab positron emission computed tomography (PET/CT) to depict human epidermal growth factor receptor 2 (HER2)-targeted tracer uptake in several metastatic sites in advanced platinum-resistant high-grade serous ovarian cancer (HGSOC). A 74-year-old woman underwent this procedure, and PET/CT images were interpreted alongside conventional biomarkers [CA125 and immunohistochemistry (IHC)] and contrast-enhanced computed tomography (CE-CT). PET imaging revealed intense tracer uptake in the primary ovarian tumour site (SUVratio 13.8), with corresponding HER2 + expression (3+) observed on the IHC of the primary tumour. Moreover, moderate uptake was observed in abdominal wall metastases (SUVratio 3.6) and near-background uptake in hepatic lesions (SUVratio 1.6), consistent with image-suggestive spatial heterogeneity in HER2-targeted tracer uptake. CA125 measurements corroborated early biochemical response, with values declining from 676 to 254 U/mL after six weeks of trastuzumab deruxtecan (T-DXd) treatment as third-line therapy. Follow-up CE-CT showed qualitative regression of [89Zr]Zr-DFO-trastuzumab-avid lesions, despite non-measurable disease by RECIST and a subsequent CE-CT imaging after 20 weeks demonstrated a mixed response pattern, without a clear relationship to pre-T-DXd [89Zr]Zr-DFO-trastuzumab uptake. This case study illustrates how integrating non-invasive [89Zr]Zr-DFO-trastuzumab PET molecular imaging with conventional radiology, IHC, and biochemical markers within the clinical pathway may support individualised therapeutic decision-making.

Background/Objectives: Radiological imaging is crucial in intensive care settings, particularly for the differential diagnosis of fever and sepsis. Computed tomography (CT) is the preferred method for detecting infectious foci in critically ill ICU patients. Methods: This study prospectively analyzed non-ECG-gated chest and abdominal CT scans from ICU patients to assess CT’s diagnostic utility. Data from prior imaging modalities (CT, radiography, MRI, ultrasound), microbiological assays (blood cultures, bronchoalveolar lavage, urinalysis), and enzymatic profiles (transaminases, pancreatic enzymes) were included. The predictive value of clinical and laboratory parameters was evaluated via correlation analysis. Results: A total of 112 patients were evaluated, with 99 exhibiting 147 inflammatory foci (92 thoracic, 55 abdominal). Definitive diagnoses were made in 58.5% of cases, while 41.5% remained classified as possible. Prior diagnostic procedures identified inflammatory origins in 57.1% of cases. Fewer CT-detected foci were observed in patients with bronchial asthma or type 2 diabetes mellitus (p = 0.049 and p = 0.006). Conclusions: CT imaging plays a central role in identifying infectious foci in ICU patients with unexplained syndromes, particularly in the thoracic region. CT scanning is recommended for sepsis management when other diagnostic evidence is lacking. Conditions such as bronchial asthma or diabetes mellitus may prompt earlier suspicion of infectious foci due to elevated inflammatory markers.

Purpose68Ga-Trivehexin is a PET tracer targeting αvβ6-integrin, a transmembrane receptor that is frequently expressed by pancreatic cancer cells. This study aimed to determine the biokinetics, image contrast, and acquisition parameters for 68Ga-Trivehexin PET imaging in pancreatic cancers.Methods44 patients with pancreatic cancer underwent Trivehexin PET/CT between June 2021 and November 2022 (EK-242052023). Biokinetics and -distribution were extracted. Previous imaging follow-up imaging, and histological findings were used as reference standards. A one-way ANOVA test, followed by Tukey HSD post-hoc test was conducted. T-tests for subgroups ± chemotherapy prior to PET were performed. Based on dynamic PET data (n = 11) recorded over 45 min, time-activity curves were generated.Results68Ga-Trivehexin PET/CT detected 40 pancreatic cancers, SUVmax 12.6; range [5.1–30.8]; 39 liver metastases, SUVmax 7.9 [2.7–16.3]; 21 lymph node metastases, SUVmax 8.6 [2.5–15.0]; 17 peritoneal metastases, SUVmax 9.5 [4.0–16.9] and 14 other metastases, SUVmax 7.2 [2.9–13.1]. Tukey post-hoc analysis revealed significant differences for SUVmax in pancreatic cancer compared to SUVmax in liver metastases [4.74, 95%-CI (1.74, 7.75)], for SUVmax in pancreatic cancer to SUVmax in lymph node metastasis [4.07, 95%-CI (0.47, 7. 67)], for tumor-to-liver ratio (TLR) of liver metastasis to TLR of pancreatic cancer [1.82, 95%-CI (0.83, 2.80)], for TLR of pancreatic cancer to TLR of peritoneal carcinomatoses [−1.88, 95%-CI (−3.15, −0.61)], and TLR of pancreatic cancer to TLR of pleural carcinomatosis [−2.79, 95%-CI (−5.42, −0.18)]. When comparing subgroups ± chemotherapy prior to PET, TLR of pancreatic cancers and TLR of peritoneal carcinomatoses were significantly different. At 45 min p.i., the highest tumor-to-backround (TBR) was observed.Conclusion68Ga-Trivehexin is suitable for imaging of αvβ6-integrin expression in pancreatic cancer due to its ability to distinguish primary carcinoma and metastases from background tissue.

Based on the results of the NETTER-1 trial, peptide receptor radionuclide therapy with Lutetium-177 (177Lu) - DOTATATE is authorized for the treatment of neuroendocrine tumors (NET) grade 1 (G1) and grade 2 (G2) of the intestine. After the failure of 177Lu-DOTATATE therapy, targeted alpha-particle therapy (TAT) may be a possible treatment option. Here, we present a patient with cancer of unknown primary NET G2 later G3. The patient was referred to our hospital with urosepsis due to a second-degree urinary retention. After stent insertion, a contrast-enhanced computed tomography revealed a huge pelvic tumor without metastases. Initially, the patient had undergone surgical treatment. Later the patient developed liver metastasis and was treated by 177Lu-DOTATATE therapy and four lines of systemic therapy. A disease progression was observed and with the knowledge of a germline BRCA1 mutation, the patient was treated with TAT (Actinium-225 [225Ac]-DOTATATE) combined with olaparib. The patient achieved a significant treatment response for 12 months indicating that a combination therapy with an alpha emitter and olaparib demands further investigations in clinical trials.

Polymethylmethacrylate (PMMA) removal during septic total joint arthroplasty revision is associated with a high fracture and perforation risk. Ultrasonic cement removal is considered a bone-preserving technique. Currently, there is still a lack of sound data on efficacy as it is difficult to detect smaller residues with reasonable technical effort. However, incomplete removal is associated with the risk of biofilm coverage of the residue. Therefore, the study aimed to investigate the efficiency of ultrasonic-based PMMA removal in a human cadaver model. The femoral components of a total hip and a total knee prosthesis were implanted in two cadaver femoral canals by 3rd generation cement fixation technique. Implants were then removed. Cement mantle extraction was performed with the OSCAR-3-System ultrasonic system (Orthofix (R)). Quantitative analysis of cement residues was carried out with dual-energy and microcomputer tomography. With a 20 mu m resolution, in vitro microcomputer tomography visualized tiniest PMMA residues. For clinical use, dual-energy computer tomography tissue decomposition with 0.75 mm resolution is suitable. With ultrasound, more than 99% of PMMA was removed. Seven hundred thirty-four residues with a mean volume of 0.40 +/- 4.95 mm(3) were identified with only 4 exceeding 1 cm in length in at least one axis. Ultrasonic cement removal of PMMA was almost complete and can therefore be considered a highly effective technique. For the first time, PMMA residues in the sub-millimetre range were detected by computer tomography. Clinical implications of the small remaining PMMA fraction on the eradication rate of periprosthetic joint infection warrants further investigations.

Ziel/Aim Das Studienziel war, den klinischen Wert von Ga-68- Trivehexin (TVH) bei der PET-Bildgebung des Pankreaskarzinoms (PDAC) zu untersuchen.

IntroductionAccurate detection and segmentation of the intraprostatic gross tumor volume (GTV) is pivotal for radiotherapy (RT) in primary prostate cancer (PCa) since it influences focal therapy target volumes and the patients’ cT stage. The study aimed to compare the performance of multiparametric resonance imaging (mpMRI) with [18F] PSMA-1007 positron emission tomography (PET) for intraprostatic GTV detection as well as delineation and to evaluate their respective influence on RT concepts.Materials and MethodsIn total, 93 patients from two German University Hospitals with [18F] PSMA-1007-PET/CT and MRI (Freiburg) or [18F] PSMA-1007-PET/MRI (Dresden) were retrospectively enrolled. Validated contouring techniques were applied for GTV-PET and -MRI segmentation. Absolute tumor volume and cT status were determined for each imaging method. The PCa distribution from histopathological reports based on biopsy cores and surgery specimen was used as reference in terms of laterality (unilateral vs. bilateral).ResultsIn the Freiburg cohort (n = 84), mpMRI and PET detected in median 2 (range: 1–5) and 3 (range: 1–8) GTVs, respectively (p < 0.01). The median GTV-MRI was significantly smaller than the GTV-PET, measuring 2.05 vs. 3.65 ml (p = 0.0005). PET had a statistically significant higher concordance in laterality with surgery specimen compared to mpMRI (p = 0.04) and biopsy (p < 0.01), respectively. PSMA PET led to more cT2c and cT3b stages, whereas cT3a stage was more pronounced in mpMRI. Based on the cT stage derived from mpMRI and PET information, 21 and 23 as well as 59 and 60 patients, respectively, were intermediate- and high-risk according to the National Comprehensive Cancer Network (NCCN) v1.2022 criteria. In the Dresden cohort (n = 9), similar results were observed.ConclusionIntraprostatic GTV segmentation based on [18F] PSMA-1007 PET results in more and larger GTVs compared to mpMRI. This influences focal RT target volumes and cT stage definition, but not the NCCN risk group.

BACKGROUND:In critically ill ICU patients, initial results showed that opposite enhancement of the adrenal glands (↑) and spleen (↓) on portal venous CT scans was associated with increased mortality over the next days to a month, with short-term mortality being best predicted. The study aimed to validate the adrenal-to-spleen ratio determined in a pilot study concerning mortality prediction.METHOD:371 portal venous CT scans of 203 ICU patients (127 men, age: 68.1 ± 14.4 years) were included in the retrospective analysis. Region-of-interest (ROI)-based Hounsfield units of the adrenal glands and the spleen and their density ratio were evaluated. The Matthews correlation coefficient (MCC) and ROC analysis were used to establish a threshold for the adrenal-to-spleen ratio regarding mortality within 72 hours of imaging. The quality of the classification of survivors and deceased patients in the current collective based on the threshold determined in a pilot study and on the current threshold was determined. The precision-recall curve (PRC) was used to test the influence of the addition of patients with low vital risk on the ROC.RESULTS:The current threshold of 1.37 for the adrenal-to-spleen ratio provides good discriminatory power between those who died and those who survived (MCC: 0.87; sensitivity: 83.7 %; specificity: 99.1 %; PPV: 93.2 %; NPV: 97.6 %) and differs only slightly from the threshold of 1.41 determined in the pilot study, which consequently has comparable discriminatory power.CONCLUSION:As a reproducible image-based prognostic marker, the portal venous adrenal-to-spleen ratio has a high predictive power for short-term death in ICU patients. It is, therefore, suitable as an indicator of high risk of death within 72 hours after imaging.KEY POINTS:· In cases of shock, CT perfusion changes of the abdominal organs can be observed.. · These changes are summarized under the term CT hypoperfusion complex.. · Organ enhancement ratios allow conclusions about the patient's short-term survival.. · The portal venous adrenal-to-spleen ratio is a sufficient prognostic mortality parameter..CITATION FORMAT:· Winzer R, Hoffmann R, Fedders D. The Portal-Venous Enhancement Ratio of the Adrenal Glands and Spleen as a Short-Term Predictor of Mortality in Intensive Care Patients. Fortschr Röntgenstr 2022; 194: 1250 - 1257.

Background: Systemic inflammation can occur after transcatheter aortic valve replacement (TAVR) and correlates with adverse outcome. The impact of remote ischemic preconditioning (RIPC) on TAVR associated systemic inflammation is unknown and was focus of this study. Methods: We performed a prospective controlled trial at a single center and included 66 patients treated with remote ischemic preconditioning (RIPC) prior to TAVR, who were matched to a control group by propensity score. RIPC was applied to the upper extremity using a conventional tourniquet. Definition of systemic inflammation was based on leucocyte count, C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6), assessed in the first 5 days following the TAVR procedure. Mortality was determined within 6 months after TAVR. RIPC group and matched control group showed comparable baseline characteristics. Results: Systemic inflammation occurred in 66% of all patients after TAVR. Overall, survival after 6 months was significantly reduced in patients with systemic inflammation. RIPC, in comparison to control, did not significantly alter the plasma levels of leucocyte count, CRP, PCT or IL-6 within the first 5 days after TAVR. Furthermore, inflammation associated survival after 6 months was not improved by RIPC. Of all peri-interventional variables assessed, only the amount of the applied contrast agent was connected to the occurrence of systemic inflammation. Conclusions: Systemic inflammation frequently occurs after TAVR and leads to increased mortality after 6 months. RIPC neither reduces the incidence of systemic inflammation nor improves inflammation associated patient survival within 6 months.

Zielsetzung Bei einer ausgeprägten Hypotonie im Rahmen eines Schocks kommt es zu Perfusionsveränderungen der abdominellen Organe, insbesondere der Milz und Nebennieren. Diese Studie evaluiert die Nebennieren/Milz-Dichterelation in der kontrastverstärkten Computertomografie (CT) als Prädiktor für die Mortalität vital gefährdeter Patienten.

BACKGROUND:Calpains are calcium activated cysteine proteases that play a pivotal role in the pathophysiology of cardiac remodeling.METHODS:Here, we performed left anterior descending coronary artery ligation in rats as a model for ischemic systolic heart failure and examined the time- and region-specific regulation of calpain-1 and calpain-2 in the left ventricular myocardium.RESULTS:Following anterior wall myocardial infarction, calpain activity was significantly increased restricted to the ischemic anterior area at days 1, 5 and 14. No changes in calpain activity at neither time point were detected in the borderzone and remote posterior area of the left ventricle. Of note, calpain activity in the infarcted anterior myocardium was regulated differentially in the acute vs. subacute and chronic phase. In the acute phase, calpain translocation to the plasma membrane and attenuation of the expression of its endogenous inhibitor, calpastatin, were identified as the driving forces. In the subacute and chronic phase, calpain activity was regulated at the level of protein expression that was shown to be essentially independent of transcriptional activity.CONCLUSIONS:We conclude that myocardial infarction leads to a distinct calpain regulation pattern in the left ventricular myocardium that is region specific and time dependent. Considering the results from our previous studies, a spatio-temporal interaction between calpains and calcium dependent natriuretic peptide production in the infarcted myocardium is possible.GENERAL SIGNIFICANCE:Our results shed more light in the differential regulation of calpain activity in the myocardium and might aid in the development of targeted post-infarct and/or heart failure therapeutics.

Introduction: To investigate the value of contrast-enhanced CT findings - splenic and aortic radiodensities and their ratios (spleno-aortic ratio) - in predicting the prognosis of critical care unit patients (CCU). Methods: One hundred thirteen continuous CCU patients with an acute deterioration (Group A: 37 women, age: 67.2 +/- 14.0 years) were included in the retrospective study. Radiodensities of the spleen and aorta were evaluated by two radiologists separately. The spleno-aortic ratio was calculated. Matthews correlation coefficient (MCC) was used in conjunction with receiver operating characteristic analysis (ROC) to assess if and which parameter was most suitable for short-term mortality prediction. The intra-class correlation coefficient assessed consensus across readers. To validate the results for the best predictor, a second cohort was evaluated (Group B: 354 CT scans). Results: The portal venous spleno-aortic ratio was best suited to predict 72-hour mortality (AUC = 0.91). A threshold ratio <= 0.53 predicted short-term mortality with a high sensitivity (80.95%) and specificity (96.74%, MCC = 0.79). The post-test probability was 85%, assuming a pre-test probability of 18.6% (72-hour mortality rate). ICCs of HU measurements in the aorta, spleen, and its ratios showed high interrater agreement (ICC: 0.92-0.99). In a control cohort, a threshold ratio <= 0.53 predicted CCU patient's outcome satisfactorily (SENS = 83.93%, SPEC = 97.65%, PPV = 87.00%, NPV = 97.00%). Conclusions: The portal venous spleno-aortic ratio serves as a distinctive imaging feature to predict short-term mortality. For CCU patients with a cut-off portal venous spleno-aortic ratio <= 0.53, the risk of dying within three days after CT scan is approximately twenty times higher.

Abstract Background The analysis aimed to compare the radiotracers [68Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 intraindividually in terms of malignant lesions, mi(molecular-imaging)TNM staging and presumable unspecific lesions retrospectively as used in routine clinical practice. Methods A retrospective analysis of 46 prostate cancer patients (median age: 71 years) who underwent consecutive [68Ga]-Ga-PSMA-11- and [18F]-F-PSMA-1007-PET/CT or PET/MRI within a mean of 12 ± 8.0 days was performed. MiTNM staging was performed in both studies by two nuclear medicine physicians who were blinded to the results of the other tracer. After intradisciplinary and interdisciplinary consensus with two radiologists was reached, differences in both malignant and presumable nonspecific tracer accumulation were analyzed. Results Differences in terms of miTNM stages in both studies occurred in nine of the 46 patients (19.6%). The miT stages differed in five patients (10.9%), the miN stages differed in three patients (6.5%), and different miM stages occurred only in one patient who was upstaged in [18F]-F-PSMA-1007 PET. Concordant miTNM stages were obtained in 37 patients (80.4%). There was no significant difference between [18F]-F-PSMA-1007 and [68Ga]-Ga-PSMA-11 in the SUVmax locally (31.5 vs. 32.7; p = 0.658), in lymph node metastases (28.9 vs. 24.9; p = 0.30) or in bone metastases (22.9 vs. 27.6; p = 0.286). In [18F]-F-PSMA-1007 PET, more patients featured presumable unspecific uptake in the lymph nodes (52.2% vs. 28.3%; p: < 0.001), bones (71.7% vs. 23.9%; p < 0.001) and ganglia (71.7% vs. 43.5%; p < 0.001). Probable unspecific, exclusively [18F]-F-PSMA-1007-positive lesions mainly occurred in the ribs (58.7%), axillary lymph nodes (39.1%) and cervical ganglia (28.3%). Conclusion In terms of miTNM staging, both tracers appeared widely exchangeable, as no tracer relevantly outperformed the other. The differences between the two tracers were far more common in presumable unspecific lesions than in malignant spots. A routinely performed two-tracer study could not be shown to be superior. Since it seems at least challenging for most nuclear medicine departments to provide both [18F]-F-PSMA-1007 and [68Ga]-Ga-PSMA-11, it appears reasonable to choose the PSMA radiotracer depending on local availability with attention to the greater occurrence of nonspecific bone findings with [18F]-F-PSMA-1007.

Einleitung Salmonelleninfektionen sind selten, werden über kontaminierte Lebensmittel fäkal-oral übertragen und führen meist zu Gastroenteritis. 5% der Patienten zeigen eine Bakteriämie, die potentiell zu Vaskulitiden führen kann. Komplikativ können daraus mykotische Pseudaneurysmata mit Rupturrisiko und hoher Mortalität entstehen. Der vorgestellte Fall beschreibt den seltenen Fall von multifokalen salmonellenbedingten penetrierenden Aortenulcera (PAUs) der Aorta.

AIM:To define reference values for the transverse relaxation rate (R2∗) in iron storage organs and to investigate the role of human haemochromatosis protein (HFE) genotype on iron storage.MATERIALS AND METHODS:Whole-body magnetic resonance imaging (MRI) including a five-echo gradient-echo sequence was performed in 483 volunteers (269 men, mean age 59.3 ± 12.2 years) without clinical evidence of an iron storage disease at 1.5 T. R2∗ values were assessed for liver, spleen, pancreas, heart, bones, and brain parenchyma. The HFE genotype was determined regarding the single nucleotide polymorphisms (SNPs) rs74315324, rs1799945, rs41303501, rs1800562, rs1800730. R2∗ values were compared among participants without and with at least one mutation. R2∗ reference values were defined using volunteers without any mutation.RESULTS:Three hundred and one participants had no mutations in any HFE SNP, 182 had at least one mutation. HFE gene mutations were distributed as (heterozygous/homozygous) rs1799945:132/9, rs1800562:33/1, and rs1800730:11/0. Mean R2∗ values ± SD (per second) in the group without mutation were: liver: 33.4 ± 12.7, spleen: 24.1 ± 13.8, pancreas: 27.2 ± 6.6, heart: 32.7 ± 11.8, bone: 69.3 ± 21.0, brain parenchyma: 13.9 ± 1.2. No significant difference in R2∗ values were found between participants with and without the HFE gene mutation for any examined iron storage organ (pliver=0.09, pspleen=0.36, ppancreas = 0.08, pheart = 0.36, pbone = 0.98, pbrain=0.74).CONCLUSION:Reference values of R2∗ in iron storage organs are feasible to support the diagnosis of iron storage diseases. Non-specific mutations in HFE SNPs appear not to affect the phenotype of tissue iron accumulation.