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Background Prostate MRI for the detection of clinically significant prostate cancer (csPCa) is standardized by the Prostate Imaging Reporting and Data System (PI-RADS), currently in version 2.1. A systematic review and meta-analysis infrastructure with a 12-month update cycle was established to evaluate the diagnostic performance of PI-RADS over time. Purpose To provide estimates of diagnostic accuracy and cancer detection rates (CDRs) of PI-RADS version 2.1 categories for prostate MRI, which is required for further evidence-based patient management. Materials and Methods A systematic search of PubMed, Embase, Cochrane Library, and multiple trial registers (English-language studies published from March 1, 2019, to August 30, 2022) was performed. Studies that reported data on diagnostic accuracy or CDRs of PI-RADS version 2.1 with csPCa as the primary outcome were included. For the meta-analysis, pooled estimates for sensitivity, specificity, and CDRs were derived from extracted data at the lesion level and patient level. Sensitivity and specificity for PI-RADS greater than or equal to 3 and PI-RADS greater than or equal to 4 considered as test positive were investigated. In addition to individual PI-RADS categories 1-5, subgroup analyses of subcategories (ie, 2+1, 3+0) were performed. Results A total of 70 studies (11 686 lesions, 13 330 patients) were included. At the patient level, with PI-RADS greater than or equal to 3 considered positive, meta-analysis found a 96% summary sensitivity (95% CI: 95, 98) and 43% specificity (95% CI: 33, 54), with an area under the summary receiver operating characteristic (SROC) curve of 0.86 (95% CI: 0.75, 0.93). For PI-RADS greater than or equal to 4, meta-analysis found an 89% sensitivity (95% CI: 85, 92) and 66% specificity (95% CI: 58, 74), with an area under the SROC curve of 0.89 (95% CI: 0.85, 0.92). CDRs were as follows: PI-RADS 1, 6%; PI-RADS 2, 5%; PI-RADS 3, 19%; PI-RADS 4, 54%; and PI-RADS 5, 84%. The CDR was 12% (95% CI: 7, 19) for transition zone 2+1 lesions and 19% (95% CI: 12, 29) for 3+0 lesions ( P = .12). Conclusion Estimates of diagnostic accuracy and CDRs for PI-RADS version 2.1 categories are provided for quality benchmarking and to guide further evidence-based patient management. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Tammisetti and Jacobs in this issue.

Individuals with psychotic disorders such as schizophrenia may be more vulnerable during pandemics, but research on this topic is limited. This study examined COVID-19 impact on a population affected by schizophrenia during the COVID-19 pandemic. Levels of psychological distress and COVID-19-related behaviours, from the COVID-related Thoughts and Behavioral Symptoms (Cov-Tabs) Scale, were compared between 107 patients with schizophrenia and 70 control participants. Participants with schizophrenia had significantly higher Cov-Tabs scores than non-clinical participants. These results suggest a higher vulnerability in this population, emphasising the need for targeted support and further assessment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Central nervous system lymphomas (CNSL) display remarkable clinical heterogeneity, yet accurate prediction of outcomes remains challenging. The IPCG criteria are widely used in routine practice for the assessment of treatment response. However, the value of the IPCG criteria for ultimate outcome prediction is largely unclear, mainly due to the uncertainty in delineating complete from partial responses during and after treatment., Methods: We explored various MRI features including semi-automated 3D tumor volume measurements at different disease milestones and their association with survival in 93 CNSL patients undergoing curative-intent treatment., Results: At diagnosis, patients with more than 3 lymphoma lesions, periventricular involvement, and high 3D tumor volumes showed significantly unfavorable PFS and OS. At first interim MRI during treatment, the IPCG criteria failed to discriminate outcomes in responding patients. Therefore, we randomized these patients into training and validation cohorts to investigate whether 3D tumor volumetry could improve outcome prediction. We identified a 3D tumor volume reduction of ≥97% as the optimal threshold for risk stratification (=3D early response, 3D_ER). Applied to the validation cohort, patients achieving 3D_ER had significantly superior outcomes. In multivariate analyses, 3D_ER was independently prognostic of PFS and OS. Finally, we leveraged prognostic information from 3D MRI features and circulating biomarkers to build a composite metric that further improved outcome prediction in CNSL., Conclusions: We developed semi-automated 3D tumor volume measurements as strong and independent early predictors of clinical outcomes in CNSL patients. These radiologic features could help improve risk stratification and help guide future treatment approaches., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The standard procedure for the diagnosis of prostate carcinoma involves the collection of 10-12 systematic biopsies (SBx) from both lobes. MRI-guided targeted biopsies (TBx) from suspicious foci increase the detection rates of clinically significant (cs) PCa. We investigated the extent to which the results of the TBx predicted the tumor board treatment decisions. SBx and TBx were acquired from 150 patients. Risk stratifications and recommendations for interventional therapy (prostatectomy and radiotherapy) or active surveillance were established by interdisciplinary tumor boards. We analyzed how often TBx alone were enough to correctly classify the tumors as well as to indicate interventional therapy and how often the findings of SBx were crucial for therapy decisions. A total of 28/39 (72%) favorable risk tumors were detected in TBx, of which 11/26 (42%) very-low-risk tumors were not detected and 8/13 (62%) low-risk tumors were undergraded. A total of 36/44 (82%) intermediate-risk PCa were present in TBx, of which 4 (9%) were underdiagnosed as a favorable risk tumor. A total of 12/13 (92%) high-risk carcinomas were detected and correctly grouped in TBx. The majority of csPCa were identified by the sampling of TBx alone. The tumor size was underestimated in a proportion of ISUP grade 1 tumors. Systematic biopsy sampling is therefore indicated for the next AS follow-up in these cases.

Objective: Persecutory ideas are highly frequent in psychotic disorders and particularly in schizophrenia. Although several measures exist to assess persecutory ideas in both clinical and non-clinical samples, there is a need for brief and psychometrically sound measures to capture the multidimensional aspects of paranoia in people diagnosed with schizophrenia. Our aim was to validate a brief version of the revised Green et al., Paranoid Thoughts Scale (R-GPTS) in schizophrenia in order to minimize time-consuming assessment., Methods: 100 individuals with schizophrenia and 72 non-clinical controls were recruited. We used the GPTS-8, a brief 8-item version of the R-GPTS recently developed and validated in the French general population. Psychometric properties of the scale were investigated including its factor structure, internal consistency, and convergent/divergent validities., Results: Confirmatory factor analysis supported the original two-factor structure (social reference and persecution subscales) of the GPTS-8. The GPTS-8 was positively and moderately correlated with the Positive and Negative Syndrome Scale (PANSS) suspiciousness item indicating good internal consistency. Concerning divergent validity, no correlations were found between the GPTS-8 and the Montreal cognitive assessment (MoCA). Importantly patients with schizophrenia reported higher scores on the GTPS-8 than controls demonstrating its clinical validity., Conclusions: The French GPTS 8-item brief scale-8 retains the psychometric strengths of the R-GPTS in schizophrenia with relevant clinical validity. The GPTS-8 can consequently be used as a short and quick measure of paranoid ideations in individuals with a diagnosis of schizophrenia., Competing Interests: Declaration of competing interest Each author confirmed that there is no conflict of interest between the author and the study., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Over the past decades, vaccination has proven to be largely beneficial to global health. Despite vaccine efficacy, the French population has been recently affected by more anti-vaccination attitudes and vaccine refusal, and it is therefore necessary to validate tools to study this health issue. The Vaccination Attitudes Examination scale (VAX) is a 12-item questionnaire targeting adults that assesses general attitudes towards vaccination. The aims of the study were to translate and adapt the original English version of the scale into French and to test the psychometric properties of the scale in a French-population-based sample of adults. We included 450 French speaking adults that completed the French VAX and other questionnaires to assess convergent and divergent validities. Exploratory and confirmatory factor analyses showed that the French version of the VAX replicated the factorial structure of the original scale. Moreover, it demonstrated high internal consistency, good convergent and divergent validities, and excellent temporal stability. Furthermore, scores on the scale differentiated vaccinees from non-vaccinee respondents. Results on the scale provide us with insight into factors involved in vaccine hesitancy in France, therefore allowing French authorities and policy makers to address these specific concerns and improve vaccine acceptance rates in this country.

Purpose: Clinical outcomes of patients with CNS lymphomas (CNSLs) are remarkably heterogeneous, yet identification of patients at high risk for treatment failure is challenging. Furthermore, CNSL diagnosis often remains unconfirmed because of contraindications for invasive stereotactic biopsies. Therefore, improved biomarkers are needed to better stratify patients into risk groups, predict treatment response, and noninvasively identify CNSL., Patients and Methods: We explored the value of circulating tumor DNA (ctDNA) for early outcome prediction, measurable residual disease monitoring, and surgery-free CNSL identification by applying ultrasensitive targeted next-generation sequencing to a total of 306 tumor, plasma, and CSF specimens from 136 patients with brain cancers, including 92 patients with CNSL., Results: Before therapy, ctDNA was detectable in 78% of plasma and 100% of CSF samples. Patients with positive ctDNA in pretreatment plasma had significantly shorter progression-free survival (PFS, P < .0001, log-rank test) and overall survival (OS, P = .0001, log-rank test). In multivariate analyses including established clinical and radiographic risk factors, pretreatment plasma ctDNA concentrations were independently prognostic of clinical outcomes (PFS HR, 1.4; 95% CI, 1.0 to 1.9; P = .03; OS HR, 1.6; 95% CI, 1.1 to 2.2; P = .006). Moreover, measurable residual disease detection by plasma ctDNA monitoring during treatment identified patients with particularly poor prognosis following curative-intent immunochemotherapy (PFS, P = .0002; OS, P = .004, log-rank test). Finally, we developed a proof-of-principle machine learning approach for biopsy-free CNSL identification from ctDNA, showing sensitivities of 59% (CSF) and 25% (plasma) with high positive predictive value., Conclusion: We demonstrate robust and ultrasensitive detection of ctDNA at various disease milestones in CNSL. Our findings highlight the role of ctDNA as a noninvasive biomarker and its potential value for personalized risk stratification and treatment guidance in patients with CNSL., [Media: see text].

Recent evidence suggests that people with schizophrenia are at high risk for severe COVID-19 and should be prioritized for vaccination. However, impaired decision-making capacities could negatively affect the uptake of COVID-19 vaccination in this population. Capacity to consent to COVID-19 vaccination was assessed in 80 outpatients with schizophrenia. Using the MacArthur Competence Assessment Tool for Treatment, 56.3% of the sample were classified as having diminished capacity to consent to the vaccination. Diminished capacity to consent to COVID-19 vaccination was associated with lower vaccination rates, poorer cognition and higher level of psychotic symptoms. Developing interventions for enhancing informed consent for vaccination is urgent within this population., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objectives: Quantitative MRI techniques, such as diffusion microstructure imaging (DMI), are increasingly applied for advanced tissue characterization. We determined its value in rotator cuff (RC) muscle imaging by studying the association of DMI parameters to isometric strength and fat fraction (FF)., Methods: Healthy individuals prospectively underwent 3T-MRI of the shoulder using DMI and chemical shift encoding-based water-fat imaging. RC muscles were segmented and quantitative MRI metrics (V-ISO, free fluid; V-intra, compartment inside of muscle fibers; V-extra, compartment outside of muscle fibers, and FF) were extracted. Isometric shoulder strength was quantified using specific clinical tests. Sex-related differences were assessed with Student's t. Association of DMI-metrics, FF, and strength was tested. A factorial two-way ANOVA was performed to compare the main effects of sex and external/internal strength-ratio and their interaction effects on quantitative imaging parameters ratios of infraspinatus/subscapularis., Results: Among 22 participants (mean age: 26.7 ± 3.1 years, 50% female, mean BMI: 22.6 ± 1.9 kg/m 2 ), FF of the individual RC muscles did not correlate with strength or DMI parameters (all p > 0.05). Subjects with higher V-intra (r = 0.57 to 0.87, p < 0.01) and lower V-ISO (r = -0.6 to -0.88, p < 0.01) had higher internal and external rotation strength. Moreover, V-intra was higher and V-ISO was lower in all RC muscles in males compared to female subjects (all p < 0.01). There was a sex-independent association of external/internal strength-ratio with the ratio of V-extra of infraspinatus/subscapularis (p = 0.02)., Conclusions: Quantitative DMI parameters may provide incremental information about muscular function and microstructure in young athletes and may serve as a potential biomarker., Key Points: • Diffusion microstructure imaging was successfully applied to non-invasively assess the microstructure of rotator cuff muscles in healthy volunteers. • Sex-related differences in the microstructural composition of the rotator cuff were observed. • Muscular microstructural metrics correlated with rotator cuff strength and may serve as an imaging biomarker of muscular integrity and function., (© 2022. The Author(s).)

Schizophrenia patients are at high risk of developing severe COVID-19 outcomes but recent evidence suggests that they are under-vaccinated. This study explored the role of potential attitudinal barriers by comparing schizophrenia patients with participants from the general population regarding COVID-19 vaccination rates, general attitudes towards vaccines, and willingness to take a COVID-19 vaccine. We conducted a cross-sectional study between April 2021 and October 2021. A total of 100 people with schizophrenia and 72 nonclinical controls were recruited. In our study, individuals with schizophrenia were under-vaccinated, despite similar general attitudes towards vaccination and higher willingness to be vaccinated against COVID-19 compared to nonclinical participants. In patients, negative attitudes toward vaccines were related to higher levels of negative psychotic symptoms and higher levels of paranoid ideation. As a whole, participants with more negative attitudes towards vaccines were less likely to be vaccinated against COVID-19 and had lower levels of trust in institutions. Vaccine hesitancy does not appear to be a major barrier for COVID-19 vaccine uptake amongst people with schizophrenia. This study suggests that disparities in COVID-19 vaccination rates in schizophrenia do not seem related to attitudinal but rather structural barriers.

Objectives: The Clinical Assessment Interview for Negative Symptoms (CAINS) is an interview-based instrument evaluating the existence and severity of negative symptoms in people diagnosed with schizophrenia or schizoaffective disorder. The aim of this study is to translate and validate a French version of the CAINS in a French sample of outpatients diagnosed with schizophrenia or schizoaffective disorder., Methods: In this study, we included 84 outpatients with a diagnosis of schizophrenia from the University Department of Adult Psychiatry in Montpellier, France. All participants were assessed for the severity of negative symptoms as well as level of depression. Psychometric properties of the French CAINS were investigated including its factor structure, internal consistency, and interrater and test-retest reliabilities. We also determined the discriminant and convergent validity., Results: Exploratory factor analysis and parallel analysis reproduced the two-factor model, and explained 43.55% of the total score variation with good internal consistency (Cronbach α of 0.87). Both interrater and test-retest reliabilities were high for the CAINS and its subscales (intraclass correlation coefficient range, 0.89-0.99). The standard errors of measurement and minimal detectable change were also investigated. Convergent validity of the CAINS was underpinned by correlations obtained with various measures of negative symptoms. Adequate discriminant validity was established by showing that the CAINS did not correlate with positive symptoms., Conclusion: Overall, our results obtained were similar to those found in the original study of the CAINS. Structural analyses also replicated the two-factor model of the CAINS. Our results indicate that the French CAINS has robust psychometric properties and is a valid tool for evaluating negative symptoms in French-speaking individuals diagnosed with schizophrenia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Laraki, Lebrun, Merenciano, Eisenblaetter, Attal, Macgregor, Decombe, Capdevielle and Raffard.)

Molecular precision oncology faces two major challenges: first, to identify relevant and actionable molecular variants in a rapidly changing field and second, to provide access to a broad patient population. Here, we report a four-year experience of the Molecular Tumor Board (MTB) of the Comprehensive Cancer Center Freiburg (Germany) including workflows and process optimizations. This retrospective single-center study includes data on 488 patients enrolled in the MTB from February 2015 through December 2018. Recommendations include individual molecular diagnostics, molecular stratified therapies, assessment of treatment adherence and patient outcomes including overall survival. The majority of MTB patients presented with stage IV oncologic malignancies (90.6%) and underwent an average of 2.1 previous lines of therapy. Individual diagnostic recommendations were given to 487 patients (99.8%). A treatment recommendation was given in 264 of all cases (54.1%) which included a molecularly matched treatment in 212 patients (43.4%). The 264 treatment recommendations were implemented in 76 patients (28.8%). Stable disease was observed in 19 patients (25.0%), 17 had partial response (22.4%) and five showed a complete remission (6.6%). An objective response was achieved in 28.9% of cases with implemented recommendations and for 4.5% of the total population (22 of 488 patients). By optimizing the MTB workflow, case-discussions per session increased significantly while treatment adherence and outcome remained stable over time. Our data demonstrate the feasibility and effectiveness of molecular-guided personalized therapy for cancer patients in a clinical routine setting showing a low but robust and durable disease control rate over time.

Cervical cancer is still the fourth most common malignancy in women worldwide and has a high mortality rate. The prognosis as well as the therapy depends largely on the extent of the tumor at the time of initial diagnosis. This shows the importance of correct staging of cervical cancer. In order to promote a globally uniform approach, staging of cervical cancer in the past was based on widespread examinations such as exam under anesthesia, histology from cervical conization or biopsy, systematic lymphadenectomy, cystoscopy, proctoscopy, i. v.-pyelogram and chest X-ray. However, as the primary tumor stage was often underestimated, the 2018 revised FIGO classification now permits cross-sectional imaging techniques and pathological findings to be incorporated into disease staging or an already existing stage to be adapted based on radiological findings. Thanks to its excellent soft tissue contrast, magnetic resonance imaging (MRI) is the method of choice for local-regional staging of cervical cancer, evaluating the response to treatment, detecting tumor recurrence and for follow-up examinations. It is important that radiologists interpreting pelvic MRI in case of suspected cervical cancer are familiar with the current FIGO staging system. This is the only way to determine the tumor stage as precisely as possible and thus lay the foundation for the success of therapy for patients. The aim of this review is to present the changes of the revised FIGO classification as well as to show the importance of MRI as the method of choice for local-regional tumor staging as a complement to clinical examination. KEY POINTS::   · Cervical cancer is still the world's fourth most common female cancer and has a high mortality rate.. · The FIGO classification for staging cervical cancer in the past was based on clinical and widespread examinations.. · The primary tumor stage has often been underestimated with the FIGO staging system since 2018.. · Since 2018, cross-sectional imaging techniques have been incorporated into disease staging.. · MRI is the method of choice for local-regional tumor staging, evaluation of the response to treatment, detection of tumor recurrence and possible complications.. CITATION FORMAT: · Merz J, Bossart M, Bamberg F et al. Revised FIGO Staging for Cervical Cancer - A New Role for MRI. Fortschr Röntgenstr 2020; 192: 937 - 944., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose:  Good training is the basis for high job satisfaction and high-quality patient care in radiology. The aim of this survey was to record the current state of working conditions for residents in radiology training in Germany and to focus on the aspects of training and psychosocial workload. The description of the actual state should help to identify possible problem areas and to develop improvement approaches., Materials and Methods:  At the beginning of 2018, we sent an electronic questionnaire to the German Roentgen Society (DRG), the German Association of Chairmen in Academic Radiology (KLR), the Chief Physician Forum of the DRG (CAFRAD) and the Forum of Registered Radiologists (FUNRAD) with the request to forward it to radiology residents. With 63 questions, the questionnaire covered seven essential areas of medical working and training conditions. In order to ensure interdisciplinary comparability, most questions were identical to previous surveys among residents of other disciplines., Results:  643 residents started the survey. 501 (78 %) questionnaires were fully processed and included in the final analysis. 65 % of respondents were satisfied with their current job situation. At the same time, shortcomings, especially with regard to the reconciliation of family and work as well as scientific and clinical work, became clear. Only 36 % of participants with children were satisfied with the compatibility of family and work at their workplace. Only 31 % of the researchers were satisfied with their research conditions. In addition, residents experienced a high psychosocial workload., Conclusion:  Job satisfaction is high among radiology residents in direct comparison to other disciplines. However, based on this survey, adjustments to working conditions and training in radiology seem necessary to maintain the health of the physicians concerned, to encourage motivation for scientific work and to enhance development opportunities, especially for women, through a better compatibility of work and family life. The present survey identifies strategies and leadership tools that can help to achieve this., Key Points:  Residents in radiology training ... · have a relatively high job satisfaction.. · experience a high psychosocial workload.. · evaluate the compatibility of family and work as in need of improvement.. · are interested in research, but evaluate research conditions as insufficient., Citation Format: · Oechtering TH, Panagiotopoulos N, Völker M et al. Work and Training Conditions of German Residents in Radiology - Results from a Nationwide Survey Conducted by the Young Radiology Forum in the German Roentgen Society. Fortschr Röntgenstr 2020; 192: 458 - 469., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Tumor development and metastasis are dependent on tumor infiltrating immune cells which form a characteristic tumor microenvironment (TME). Activated monocytes secrete the protein heterodimer S100A8/A9 promoting TME formation. Monocyte-dependent proteases facilitate local tumor cell invasion by degradation of the extracellular matrix. We aimed for target specific in vivo imaging of S100A8 and proteases to provide differentiating biomarkers for local tumor growth and metastatic potential., Procedures: Murine breast cancer cells of the 4T1 model with graduated metastatic potential (4T1 and 4T07: both hematogenous metastasis > 168FAR: lymph-node metastasis > 67NR: no metastasis) were orthotopically implanted into female BALB/c mice. At 4 mm size, tumors were investigated by injecting the protease-specific probe ProSense 750EX (PerkinElmer, 4T1 n = 7, 4T07 n = 10, 168FAR n = 16, 67NR n = 15) and anti-S100A8-Cy5.5 (n = 6 each) and performing fluorescence reflectance imaging at 0 and 24 h after injection. In vivo imaging was validated with immunohistochemistry., Results: At 24 h, S100A8-specific signals in 4T1 and 4T07 were significantly higher (1714.05/1683.45 AU) as compared to 168FAR and 67NR (174.85/167.95 AU, p = 0.0012/p = 0.0003), reflecting the capability of hematogenous spread. Protease-specific signals were significantly higher in 4T1 and 4T07 (348.01/409.93 AU) as compared to 168FAR (214.91 AU) and 67NR (129.78 AU p < 0.0001 each), reflecting local vessel invasion and tumor cell shedding. Immunohistology supported the in vivo imaging results., Conclusions: Non-invasive in vivo imaging of S100A8 and monocytic proteases allows for differentiation of the tumors' local invasive and systemic metastatic potential in reflecting the TME formation. While proteases augment local tumor cell invasion, solid metastases seem to be dependent on a pro-tumoral microenvironment.

Tumor development and growth, as well as metastatic spread, are strongly influenced by various, mostly innate, immune cells, which are recruited to the tumor site and driven to establish a specific tumor-supportive microenvironment. The contents of this microenvironment, such as myeloid cells, are a major factor in the overall prognosis of malignant disease, addressed by a constantly growing armament of therapeutic interventions targeting tumor-supportive immune cells. Current clinical imaging has long ignored the growing need for diagnostic approaches addressing these microenvironmental contents-approaches enabling a sensitive and specific classification of tumor immune crosstalk and the resulting tumor-associated immune cell activity. In this focus article we review the present status of, and promising developments in, the in vivo molecular imaging of tumor immune components designed to allow for inferences to be made on the cross-talk between tumor cells and the immune system. Current imaging modalities based on the infiltrating cell types are briefly discussed., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Background Systemic cancer spread is preceded by the establishment of a permissive microenvironment in the target tissue of metastasis - the premetastatic niche. As crucial players in establishment of the pre-metastatic niche, myeloid derived suppressor cells (MDSC) release S100A8/A9, an exosomal protein that contributes to metastasis, angiogenesis, and immune suppression. We report the application of antibody-based single-photon emission computed tomography (SPECT) for detection of S100A8/A9 in vivo as an imaging marker for pre-metastatic tissue priming. Methods A syngeneic model system for invasive breast cancer with (4T1.2) or without (67NR) the tendency to form lung metastasis was established in BALB/c mice. A SPECT-probe has been generated and tested for visualization of S100A9 release. Tumor-associated changes in numbers and fuction of immune cells in pre-metastatic tissue were evaluated by flow cytometry and confocal microscopy. Results S100A8/A9 imaging reflected MDSC abundance and the establishment of an immunosuppressive environment in pre-metastatic lung tissue (activity 4T1.2 vs. healthy control: 0.95 vs. 0.45 %ID; p<0.001). The S100A8/A9 imaging signal in the pre-metastatic lung correlated with the subsequent metastatic tumor burden in the same organ (r 2 =0.788; p<0.0001). CCL2 blockade and the consecutive inhibition of premetastatic niche establishment was clearly depicted by S100A9-SPECT (lung activity untreated vs. treated: 2 vs, 1.4 %ID). Conclusion We report S100A8/A9 as a potent imaging biomarker for tumor-mediated immune remodeling with potential applications in basic research and clinical oncology., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Unlabelled: Locoregional recurrence of breast cancer poses significant clinical problems because of frequent inoperability once the chest wall is involved. Early detection of recurrence by molecular imaging agents against therapeutically targetable receptors, such as c-Met, would be of potential benefit. The aim of this study was to assess (18)F-AH113804, a peptide-based molecular imaging agent with high affinity for human c-Met, for the detection of early-stage locoregional recurrence in a human basal-like breast cancer model, HCC1954., Methods: HCC1954 tumor-bearing xenograft models were established, and (18)F-AH113804 was administered. Distribution of radioactivity was determined via PET at 60 min after radiotracer injection. PET and CT images were acquired 10 d after tumor inoculation, to establish baseline distribution and uptake, and then on selected days after surgical tumor resection. CT images and caliper were used to determine the tumor volume. Radiotracer uptake was assessed by (18)F-AH113804 PET imaging. c-Met expression was assessed by immunofluorescence imaging of tumor samples and correlated with (18)F-AH113804 PET imaging results., Results: Baseline uptake of (18)F-AH113804, determined in tumor-bearing animals after 10 d, was approximately 2-fold higher in the tumor than in muscle tissue or the contralateral mammary fat pad. The tumor growth rate, determined from CT images, was comparable between the animals with recurrent tumors, with detection of tumors of low volume (<10 mm(3)) only possible by day 20 after tumor resection. (18)F-AH113804 PET detected local tumor recurrence as early as 6 d after surgery in the recurrent tumor-bearing animals and exhibited significantly higher (18)F-AH113804 uptake (in comparison to mammary fatty tissue), with a target-to-background (muscle) ratio of approximately 3:1 (P < 0.01). The c-Met expression of individual resected tumor samples, determined by immunofluorescence, correlated with the respective (18)F-AH113804 imaging signals (r = 0.82, P < 0.05)., Conclusion: (18)F-AH113804 PET provides a new diagnostic tool for the detection of c-Met-expressing primary tumor and has potential utility for the detection of locoregional recurrence from an early stage., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: Tumors recruit and reprogram immune cells to support tumor development and spread, the most prominent among them being of monocytic origin such as tumor-associated macrophages (TAM) or myeloid-derived suppressor cells (MDSC). The alarmin S100A8/A9 has been implicated in the induction of TAM and MDSC. We assessed S100A9 as a molecular imaging marker for the activity of tumor-associated immune cells in a syngeneic murine breast cancer model. S100A9 could serve as a surrogate marker for tumor immune crosstalk as a function of malignancy, providing a tool with the potential for both basic research in tumor immunology and clinical stratification of patients., Methods: BALB/c mice were inoculated with murine breast cancer cells of common origin but different metastatic capability. At different times during tumor development, optical imaging was performed using a S100A9-specific probe to visualize activated monocytes. To further explore the impact of tumor-educated monocytes, splenic myeloid cells were isolated from either healthy or tumor-bearing animals and injected into tumor-bearing mice. We analyzed the effect of the cell transfer on immune cell activity and tumor development., Results: We could prove S100A9-driven imaging to sensitively and specifically reflect monocyte activity in primary tumor lesions. The imaging results were corroborated by histology and fluorescence-activated cell sorting analyses. In a prospective experiment, S100A9 imaging proved indicative of the individual tumor growth, with excellent correlation. Moreover, we could show that the monocyte activity as depicted by S100A9 activity in the primary tumor lesion mirrored the tumor's metastatic behavior. Treatment with tumor-primed splenic monocytes induced increased tumor growth, accompanied by an augmented infiltration of activated myeloid cells (MDSC and TAM) into the tumor. The consecutive S100A9 expression as depicted by in vivo imaging was significantly increased., Conclusion: S100A9 proved to be a sensitive and specific marker for the activity of tumor-associated immune cells. To our knowledge, S100A9 imaging represents a first in vivo imaging approach for the estimation of recruitment and activity of tumor-associated myeloid immune cells. We demonstrated the potential value of this imaging approach for prediction of local and systemic tumor development., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)