This study aimed to externally validate the P-Score, a composite scoring system combining PI-RADS and PRIMARY score, for its diagnostic accuracy in detecting clinically significant (ISUP ≥ 2) and higher-grade (ISUP ≥ 3) prostate cancer (PCa). 230 biopsy-naïve men with suspected PCa were prospectively enrolled in the DEPROMP trial and underwent multiparametric MRI and [68Ga]Ga-DKFZ-PSMA-11 PET/CT. Lesions were assessed using PI-RADS v2.1, the PRIMARY score, and the derived P-Score. Targeted biopsies were guided by imaging findings, and histopathology served as the reference standard. Diagnostic performance was evaluated using receiver operating characteristic curve analyses and DeLong’s test to compare the area under the curve (AUC) between scoring systems. For clinically significant PCa (ISUP ≥ 2), no significant difference in diagnostic performance was observed between the P-Score (AUC 0.796) and PI-RADS (AUC 0.804; p = 0.72), whereas the P-Score significantly outperformed the PRIMARY score (AUC 0.730; p < 0.001). Similarly, for detection of ISUP ≥ 3 disease, no significant difference in diagnostic performance was observed between the P-Score (AUC 0.840) and PI-RADS (AUC 0.830; p = 0.66). In the PI-RADS 3 subgroup, diagnostic performance remained limited, with AUCs of 0.573 (95

68Ga-PSMA-11 PET/CT (PSMA PET/CT) is used for staging advanced prostate cancer (PCa); however, its role in initial cancer detection and guiding localized treatment remains uncertain. The primary objective of this study was to assess the impact of upfront PSMA PET/CT on treatment decision-making based on imaging and biopsy-derived information. Methods: In this prospective, phase 2 interventional trial, 230 biopsy- and imaging-naïve men with suspected PCa underwent PSMA PET/CT and multiparametric MRI (mpMRI) before targeted ultrasound fusion and systematic biopsy. Randomized assessor teams independently reviewed histopathology and imaging data from either the mpMRI or the combined mpMRI plus PSMA PET/CT pathway and formulated treatment plans accordingly. Patient recruitment was conducted between 2021 and 2023. Results: Among 137 patients with PCa (9% low-, 35% intermediate-, and 15% high-risk disease), PSMA PET/CT altered management plans in 34% of patients, primarily modifying local treatment strategies, including lymph node dissection (16%), a nerve-sparing procedure (18%), and radiation field adjustments (28%). Systemic therapy escalation was rare (1%). In addition, 2% of patients initiated active treatment, 5% received adjunctive hormone therapy, and 7% underwent metastasis-directed therapy. Upfront PSMA PET/CT prompted treatment intensification at comparable rates in both intermediate-risk (31%) and high-risk (30%) PCa with high interrater agreement (Cohen κ, 0.71; 95% CI, 0.61-0.80). Prostate-specific antigen density of at least 0.15 ng/mL3 (odds ratio, 2.48; 95% CI, 1.22-5.06) and abnormal digital rectal examination (odds ratio, 2.12; 95% CI, 1.03-4.33) predicted PSMA PET/CT-driven changes. Conclusion: Early PSMA PET/CT staging altered treatment strategies for up to one third of patients with intermediate- and high-risk PCa by enhancing metastasis detection and local tumor characterization. Its effect on oncologic and functional outcomes warrants further investigation.

BACKGROUND:Assessing disease activity in giant cell arteritis (GCA) remains challenging, as existing clinical, laboratory and imaging biomarkers lack specificity. This proof-of-concept study explored the diagnostic potential of vascular adhesion protein-1 (VAP-1) targeting [68Ga]Ga-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) DOTA-sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) positron emission tomography-CT (PET/CT) as an inflammation-specific molecular imaging biomarker in newly diagnosed and relapsing GCA. METHODS:Patients with newly diagnosed GCA underwent [68Ga]Ga-DOTA-Siglec-9 PET/CT and vascular ultrasound. Tracer uptake (SUVmean/SUVmax) was quantified in aortic, supra-aortic and extravascular (shoulder/hip) regions and compared with relapsing patients. Levels of soluble VAP-1 (sVAP-1) and matrix metalloproteinase (MMP)2/MMP3/MMP9 were measured in patients and controls as potential biomarkers related to vascular inflammation. RESULTS:Eight patients with newly diagnosed GCA were compared with eight relapsing patients, alongside eight controls. Imaging revealed a positive association between ultrasound-assessed subclavian artery intima-media thickness and tracer uptake (r=0.67, p=0.035). Prednisolone exposure was inversely associated with vascular uptake across various vascular regions, with SUVmean showing a stronger overall negative association than SUVmax (SUVmean r=-0.51, p=0.043; SUVmax r=-0.62, p=0.010). Levels of sVAP-1 were reduced in newly diagnosed GCA compared with relapsing patients (p=0.0145) and controls (p=0.0446), and inversely associated with MMP2 (r=-0.56, p=0.037) and MMP9 (r=-0.47, p=0.089). Notably, MMP2 and MMP3 were negatively associated with vascular uptake (eg, aortic arch: r=-0.59, p=0.027). CONCLUSIONS:This first-in-human study demonstrates that [68Ga]Ga-DOTA-Siglec-9 PET/CT detects vascular inflammation in GCA and shows attenuation with prednisolone exposure. Reduced sVAP-1 levels and inverse associations between MMP2/MMP3 and tracer uptake support a functional VAP-1/MMP axis underlying the imaging signal. Our findings further position [68Ga]Ga-DOTA-Siglec-9 PET/CT as a promising potential molecular imaging biomarker in GCA.

Background Harmonizing institutional Standard Operating Procedures (SOPs) with international PET/CT guidelines is complex and resource intensive. This study evaluates the ‘Action Corridor’ model for structured ‘to-be’/‘as-is’ comparison and assesses a generative AI-assisted workflow for extracting quality-relevant parameters from heterogeneous documentation in a single-centre setting. Methods Current EANM/SNMMI guidelines were systematically compared with institutional SOPs for [18F]FDG, [68Ga]Ga-PSMA, and [68Ga]Ga-DOTATOC PET/CT using a four-category framework (Conformity, Specification, Justified Adaptation, Potential Inconsistency). A generative AI model extracted predefined quantitative parameters from unstructured SOPs. AI-extracted values were cross-checked against independent human review. Results Overall harmonisation was high across protocols. Quantitative deviations were mainly observed in uptake times (practice-to-guideline ratios 0.41–0.75), most pronounced for [68Ga]Ga-DOTATOC (30 min vs. 55–90 min). Reduced effective radiation exposure was achieved for [18F]FDG (ratio 0.83). No discrepancies were identified in the predefined quantitative parameters compared with human verification. Conclusion The ‘Action Corridor’ model enables transparent identification of guideline–practice deviations while preserving justified local adaptations. Generative AI reliably supports structured parameter extraction in quality management workflows. In this single-centre proof-of-concept setting, the framework demonstrates methodological feasibility. Empirical scalability across institutions requires prospective multicentre validation.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a promising, noninvasive therapeutic approach for essential tremor (ET), yet the effects of the respective lesions on functional brain network organization remain poorly understood. Here, we performed graph theory analysis to investigate changes in small-world properties and modular architecture in ET patients six months after unilateral MRgFUS of the thalamic ventral intermediate (VIM) nucleus. Small-worldness and normalized clustering coefficient increased significantly after MRgFUS, while clustering coefficient, characteristic path length, normalized characteristic path length, global efficiency, and local efficiency remained unchanged. Modular organization was largely preserved, but trend-level enhancements in inter-modular connectivity were observed between frontoparietal and subcortical modules, as well as between frontoparietal and frontotemporal-parietal modules. Within these modules, betweenness centrality increased significantly in specific cortical hubs, including the left superior frontal gyrus, right superior parietal lobule, and left postcentral gyrus. These findings indicate that unilateral VIM-MRgFUS induces selective functional network reorganization, particularly affecting relative clustering and nodal centrality patterns.

BACKGROUND:Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy alleviates tremor in tremor-dominant Parkinson's disease (TD-PD). However, its effects on the functional network topology remain unclear. METHODS:Twenty-one TD-PD patients underwent unilateral MRgFUS thalamotomy and clinical and MRI assessments. For the overall cohort, graph theory analysis was employed to examine differences in small-world properties and modular structure between baseline and 6 months after MRgFUS. Changes in topological properties were assessed using paired t-tests or Wilcoxon tests, and their associations with clinical improvement. Additionally, subgroup analyses were performed on responder (n = 10) and relapser (n = 9) data. RESULTS:Tremor scores decreased significantly after MRgFUS contralateral to the lesioned thalamus. Significant increases were observed in small-worldness and normalized clustering coefficient after MRgFUS. Inter-modular connectivity showed trend-level enhancement between cortical-basal ganglia and thalamic modules, and between cerebellar and temporal-hippocampal modules. In responder, significant increases were observed in small-worldness, normalized clustering coefficient, and global efficiency, whereas characteristic path length showed a significant decrease. Changes in global efficiency and characteristic path length were significantly correlated with clinical improvement. CONCLUSION:MRgFUS thalamotomy for TD-PD induced partial reorganization of small-world properties, indicating a shift toward a more integrated network topology, especially in responder. Changes correlated with tremor reduction and improved functional disability, highlighting that effective treatment impacts on global network integration.

Skeletal muscle radiodensity (SMD) is an emerging imaging-derived marker of muscle quality. Its prognostic relevance in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy has not yet been systematically evaluated. This study aims to investigate the prognostic value of SMD derived from routine pretherapeutic PET/CT imaging in a large real-world mCRPC cohort treated with [¹⁷⁷Lu]Lu-PSMA-617. In this single-center study, the largest to date cohort comprising 410 mCRPC patients was analyzed. SMD was quantified automatically from the L3-level CT component of pretherapeutic [⁶⁸Ga]Ga-PSMA-PET/CT using an AI-based segmentation tool. An optimal SMD cut-off (19.26 HU) was determined for survival stratification. Associations with overall survival (OS) were assessed using multivariable Cox regression (univariable and multivariable, adjusted for baseline PSA) and Kaplan-Meier analysis. Lower SMD was associated with reduced OS (HR 1.87, P<.001). Median OS were significantly shorter in the SMD-low group compared to the SMD-high group (7.6 months vs. 12.2 months; P<.001). This prognostic stratification was seen in both, patients with or without PSA50 or PSA90 response, respectively. SMD correlated with age, albumin, and PSA, but not with BMI. SMD assessed from routine pretherapeutic PET/CT is a non-invasive prognostic biomarker in patients undergoing PSMA-targeted radioligand therapy. Integration of host-derived imaging biomarkers such as SMD with tumor-specific parameters may improve risk stratification, prehabilitation and support future individualized treatment strategies in advanced prostate cancer.

This study aimed to clarify the renal safety of [177Lu]Lu-PSMA-617 for metastatic castration-resistant prostate cancer (mCRPC), addressing emerging reports of nephrotoxicity. Methods: We retrospectively analyzed patients with mCRPC from the real-world LUMEN registry who received 3 or more cycles of [177Lu]Lu-PSMA-617. The endpoint was the change in estimated glomerular filtration rate (eGFR) over 24 mo, assessed using linear mixed-effects models. Results: Analysis of 261 patients revealed a modest average decline in eGFR of -0.15 mL/min/1.73 m2 per month (95% CI, -0.25 to -0.05; P = 0.005), translating to -1.80 mL/min/1.73 m2 per year (95% CI, -3.03 to -0.57). The rate of loss accelerated by approximately -0.1 per year per additional gigabecquerel of administered activity (95% CI, -0.18 to -0.01; P = 0.028). Conclusion: [177Lu]Lu-PSMA-617 is associated with a slight long-term average decline in eGFR. Although this is unlikely to be clinically relevant for late-stage mCRPC, the cumulative dose effect warrants careful monitoring in earlier disease stages.

[177Lu]Lu-PSMA-617 is a standard-of-care therapy for metastatic castration-resistant prostate cancer (mCRPC). Given the heterogeneous clinical responses, accessible prognostic tools are needed. We recently demonstrated that the Bellmunt Risk Score (BRS)—comprising ECOG performance status >0, hemoglobin <10 g/dL, and the presence of liver metastases—predicts overall survival (OS) in a primary mCRPC cohort. This study aims to externally validate the BRS in an independent cohort. We retrospectively evaluated 243 mCRPC patients treated with [177Lu]Lu-PSMA-617 at an independent tertiary center. The BRS was calculated at baseline (range 0-3). Endpoints included OS analyzed via Kaplan-Meier estimators, multivariable Cox regression, Harrell’s C-index, and time-dependent area under the curve (tAUC). The cohort was distributed into BRS 0 (17.6

Abstract Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an established thermoablative treatment for tremor. Although outcomes in Essential Tremor approach those of deep brain stimulation, efficacy in tremor-dominant Parkinson’s disease (TDPD) is often less durable, with tremor relapse reported in 30-50% of cases. Previous associations with lesion size or age remain descriptive and do not explain why anatomically similar lesions yield divergent long-term outcomes. We retrospectively analyzed 20 patients with TDPD who underwent unilateral MRgFUS. Lesions were used as seeds for normative structural and functional connectivity analyses. Durable tremor control was associated with lesion showing stronger functional connectivity to primary motor (M1), primary somatosensory (S1), and supplementary motor areas, as well as inferior frontal and occipital cortices. In contrast, relapse was linked to greater connectivity with cerebellar motor and associative regions. Structurally, optimal lesions converged at the triangular interface of the nuclei ventralis intermedius, ventralis oralis, and ventro caudalis. Streamlines associated with better outcomes projected posteriorly towards S1, with M1 delineating an anterior functional boundary beyond which outcomes declined. Structural fingerprints emphasized posterior sensorimotor areas as critical therapeutic outputs. Findings define a connectivity-based substrate of durable tremor suppression and support the development of individualized, network-guided targeting strategies for MRgFUS in TDPD.

Uterine fibroids often lead to symptoms that negatively impact health-related quality of life (HRQOL). High-intensity focused ultrasound (HIFU) has emerged as a promising noninvasive treatment for reducing fibroid size and symptoms. The Mirabilis system for ultrasound (US)-guided HIFU introduces a novel technique known as ‘shell ablation’. This study evaluates the feasibility and efficacy of Mirabilis in a clinical setting, focusing on clinical outcomes. Sixteen patients with 23 uterine fibroids were treated with the Mirabilis system. Follow-up assessments included US and MRI at baseline, 6 weeks, 3, 6 and 9 months, and 1 year after HIFU. Changes in symptoms and QOL were evaluated using the Uterine Fibroid Symptom and HRQOL Questionnaire. A significant reduction in fibroid volume was observed after HIFU (baseline 182.1 ± 49.3 ml; 1 year: 76.0 ± 37.9 ml, p < 0.001). The symptom severity score significantly declined (baseline 57.2 ± 3.8; 1 year: 30.2 ± 4.9, p < 0.001), correlating with a significant improvement in HRQOL (baseline 47.0 ± 3.9, 1 year: 71.8 ± 5.3, p < 0.001). HIFU with the portable Mirabilis system is a feasible and safe noninvasive treatment for symptomatic uterine fibroids in an outpatient setting. This approach allows efficient and rapid ablation even for large fibroids, significantly reducing fibroid volume and symptoms.

Neuroendocrine tumors (NETs) are a heterogeneous group of malignancies characterized by variable immune microenvironment. This study aimed to analyze the infiltration of NETs by CD68+ tumor-associated macrophages (TAMs) and FoxP3+ regulatory T cells (Tregs) using Qupath software for semi-automated histopathological quantificationThirty-two patients with resected NETs were included. CD68 and FoxP3 expression were assessed by immunohistochemistry followed by automated cell detection and spatial analysis.The mean percentage of CD68+ cells was 0.35%, with no significant differences between pancreatic and gastrointestinal NETs. FoxP3+ cells were less frequent (mean: 0.06%), with higher levels in gastrointestinal NETs compared to pancreatic NETs (p < 0.05). Kaplan-Meier analysis revealed that CD68+ cells showed a trend to positive correlation with progression-free survival (PFS) and overall survival (OS). Thereby, patients exceeding a 0.1% CD68+ cell threshold exhibited longer survival (PFS: not reached vs. 106 months). In contrast, FoxP3+ cells showed a trend to inverse correlation with survival; patients with >0.05% FoxP3+ cells had shorter PFS (36 months vs. 147 months) and OS (180 months vs. not reached). Multivariate Cox regression identified N-stage as the sole predictor of OS. CD68+ TAM density was not associated with other clinical parameters, while FoxP3+ cell infiltration correlated significantly with venous invasion and advanced N- and M-stages.These findings highlight the potential prognostic relevance of immune cell infiltration in NETs and underscore the utility of Qupath for quantifying immune markers in histopathological analyses. The contrasting roles of CD68+ TAMs and FoxP3+ Tregs in the NET microenvironment warrant further exploration to inform immunotherapeutic strategies.

[177Lu]Lu-PSMA-617 therapy has emerged as a promising radioligand treatment for metastatic castration-resistant prostate cancer (mCRPC). Given the overall poor prognosis of mCRPC, accurately predicting the key endpoint overall survival (OS) remains an ongoing challenge, crucial for optimizing risk/benefit assessment prior to treatment. This study investigates the prognostic utility of the simple designed Bellmunt Risk Score (BRS) in mCRPC patients treated with [177Lu]Lu-PSMA-617. We retrospectively evaluated data from 386 mCRPC patients who had received [177Lu]Lu-PSMA-617 therapy at our center. BRS was constructed by attributing one point for each of the following risk factors: ECOG performance status (ECOG PS) > 0, hemoglobin < 10 g/dL, and the presence of liver metastases. Additionally, an enhanced version of the score including C-reactive protein (CRP) > 30 mg/dL and a modified version utilizing a semi-quantitative ECOG PS were developed. Statistical analysis included Cox regression, Kaplan-Meier estimates, concordance indices and time-dependent area under the curve (tAUC). The BRS served as an independent predictor of OS in multivariable analysis. The estimated median OS was 17.6, 10.9, 6.6, and 2.7 months for patients with scores of 0, 1, 2 and 3, respectively (Log-Rank P < 0.001). The tAUC values for predicting 1-year and 2-year OS were 71.6% and 74.4%, respectively. The CRP-enhanced score further improved prognostic accuracy, achieving tAUCs of 75.7% for 1-year OS and 78.1% for 2-year OS. The Bellmunt Risk Score effectively stratifies mCRPC patients undergoing [177Lu]Lu-PSMA-617 therapy. Its straightforward design, based on readily accessible clinical parameters, ensures practicality and utility in real-world clinical settings.