CT-guided High-Dose-Rate Brachytherapy versus Transarterial Chemoembolization in Patients with Unresectable Hepatocellular Carcinoma.

Background CT-guided high-dose-rate (HDR) brachytherapy (hereafter, HDR brachytherapy) has been shown to be safe and effective for patients with unresectable hepatocellular carcinoma (HCC), but studies comparing this therapy with other local-regional therapies are scarce. Purpose To compare patient outcomes of HDR brachytherapy and transarterial chemoembolization (TACE) in patients with unresectable HCC. Materials and Methods This multi-institutional retrospective study included consecutive treatment-naive adult patients with unresectable HCC who underwent either HDR brachytherapy or TACE between January 2010 and December 2022. Overall survival (OS) and progression-free survival (PFS) were compared between patients matched for clinical and tumor characteristics by propensity score matching. Not all patients who underwent TACE had PFS available; thus, a different set of patients was used for PFS and OS analysis for this treatment. Hazard ratios (HRs) were calculated from Kaplan-Meier survival curves. Results After propensity matching, 150 patients who underwent HDR brachytherapy (median age, 71 years [IQR, 63-77 years]; 117 males) and 150 patients who underwent TACE (OS analysis median age, 70 years [IQR, 63-77 years]; 119 male; PFS analysis median age, 68 years [IQR: 63-76 years]; 119 male) were analyzed. Hazard of death was higher in the TACE versus HDR brachytherapy group (HR, 4.04; P < .001). Median estimated PFS was 32.8 months (95% CI: 12.5, 58.7) in the HDR brachytherapy group and 11.6 months (95% CI: 4.9, 22.7) in the TACE group. Hazard of disease progression was higher in the TACE versus HDR brachytherapy group (HR, 2.23; P < .001). Conclusion In selected treatment-naive patients with unresectable HCC, treatment with CT-guided HDR brachytherapy led to improved OS and PFS compared with TACE. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Chapiro in this issue.

Myocardial Late Gadolinium Enhancement (LGE) in Cardiac Magnetic Resonance Imaging (CMR)-An Important Risk Marker for Cardiac Disease.

Cardiovascular magnetic resonance (CMR) has significantly revolutionized the comprehension and diagnosis of cardiac diseases, particularly through the utilization of late gadolinium enhancement (LGE) imaging for tissue characterization. LGE enables the visualization of expanded extracellular spaces in conditions such as fibrosis, fibrofatty tissue, or edema. The growing recognition of LGE's prognostic capacity underscores its importance, evident in the increasing explicit recommendations within guidelines. Notably, the contemporary characterization of cardiomyopathies relies on LGE-based scar assessment by CMR to a large extent. This review describes the pattern and prognostic value of LGE in detail for various cardiac diseases. Despite its merits, establishing LGE as a reliable risk marker encounters challenges. Limitations arise from the fact that not all diseases show LGE, and it should always be analyzed in the context of all CMR sequences and the patient's medical history. In summary, LGE stands as a robust indicator of adverse outcomes in diverse cardiovascular diseases. Its further integration into routine practice is desirable, necessitating widespread availability and application to accumulate both individual and scientific experience.

[Emergency diagnoses in the gastrointestinal tract]. / Notfalldiagnosen im Gastrointestinaltrakt.

Gastrointestinal emergencies are a frequent reason for presentation in the emergency department and involve patients of all ages. The patients must undergo an immediate cross-sectional imaging as in many cases the underlying pathology is a life-threatening condition, which often needs surgical or in some cases also interventional radiological treatment. In this overview, the most important differential diagnoses and their characteristics on cross-sectional imaging are presented.

Identification of impactful imaging biomarker: Clinical applications for breast and prostate carcinoma. / Ermittlung aussagekräftiger Bildgebungsbiomarker: Klinische Anwendungen bei Mamma- und Prostatakarzinomen.

BACKGROUND: Imaging biomarkers are quantitative parameters from imaging modalities, which are collected noninvasively, allow conclusions about physiological and pathophysiological processes, and may consist of single (monoparametric) or multiple parameters (bi- or multiparametric). METHOD: This review aims to present the state of the art for the quantification of multimodal and multiparametric imaging biomarkers. Here, the use of biomarkers using artificial intelligence will be addressed and the clinical application of imaging biomarkers in breast and prostate cancers will be explained. For the preparation of the review article, an extensive literature search was performed based on Pubmed, Web of Science and Google Scholar. The results were evaluated and discussed for consistency and generality. RESULTS AND CONCLUSION: Different imaging biomarkers (multiparametric) are quantified based on the use of complementary imaging modalities (multimodal) from radiology, nuclear medicine, or hybrid imaging. From these techniques, parameters are determined at the morphological (e. g., size), functional (e. g., vascularization or diffusion), metabolic (e. g., glucose metabolism), or molecular (e. g., expression of prostate specific membrane antigen, PSMA) level. The integration and weighting of imaging biomarkers are increasingly being performed with artificial intelligence, using machine learning algorithms. In this way, the clinical application of imaging biomarkers is increasing, as illustrated by the diagnosis of breast and prostate cancers. KEY POINTS: · Imaging biomarkers are quantitative parameters to detect physiological and pathophysiological processes.. · Imaging biomarkers from multimodality and multiparametric imaging are integrated using artificial intelligence algorithms.. · Quantitative imaging parameters are a fundamental component of diagnostics for all tumor entities, such as for mammary and prostate carcinomas.. CITATION FORMAT: · Bäuerle T, Dietzel M, Pinker K et al. Identification of impactful imaging biomarker: Clinical applications for breast and prostate carcinoma. Fortschr Röntgenstr 2024; 196: 354 - 362.

A Machine Learning Framework Reduces the Manual Workload for Systematic Reviews of the Diagnostic Performance of Prostate Magnetic Resonance Imaging.

Prostate magnetic resonance imaging has become the imaging standard for prostate cancer in various clinical settings, with interpretation standardized according to the Prostate Imaging Reporting and Data System (PI-RADS). Each year, hundreds of scientific studies that report on the diagnostic performance of PI-RADS are published. To keep up with this ever-increasing evidence base, systematic reviews and meta-analyses are essential. As systematic reviews are highly resource-intensive, we investigated whether a machine learning framework can reduce the manual workload and speed up the screening process (title and abstract). We used search results from a living systematic review of the diagnostic performance of PI-RADS (1585 studies, of which 482 were potentially eligible after screening). A naïve Bayesian classifier was implemented in an active learning environment for classification of the titles and abstracts. Our outcome variable was the percentage of studies that can be excluded after 95% of relevant studies have been identified by the classifier (work saved over sampling: WSS@95%). In simulation runs of the entire screening process (controlling for classifier initiation and the frequency of classifier updating), we obtained a WSS@95% value of 28% (standard error of the mean ±0.1%). Applied prospectively, our classification framework would translate into a significant reduction in manual screening effort. Patient summary: Systematic reviews of scientific evidence are labor-intensive and take a lot of time. For example, many studies on prostate cancer diagnosis via MRI (magnetic resonance imaging) are published every year. We describe the use of machine learning to reduce the manual workload in screening search results. For a review of MRI for prostate cancer diagnosis, this approach reduced the screening workload by about 28%.

Development, synthesis and evaluation of novel fluorescent Endothelin-B receptor probes.

The endothelin (ET) signaling system is comprised of three endothelin peptides (ET-1, -2 and -3) and two corresponding endothelin-A and -B receptors (ETAR and ETBR), which belong to the G-protein coupled receptor (GPCR) superfamily. The endothelin axis, as this system is also referred to, contributes to the maintenance of vascular tone, functions as regulator of inflammation and proliferation and helps in balancing water homeostasis. In pathological settings, the ET axis is known to contribute to endothelial activation in cardiovascular diseases, to cell proliferation, chemoresistance and metastasis in cancer and to inflammation and fibrosis in renal disease. Antagonists of ETAR and ETBR, either subtype-specific compounds or substances with high affinity to both receptors, have been developed for more than 30 years. In the preclinical context, in vivo imaging of endothelin receptor expression has been utilized to assess ET-axis contribution to e.g. cancer or myocardial infarction. In this work, we present the development and synthesis of two novel ETBR-specific fluorescent probes, based on the available antagonists BQ788 and IRL2500 and their preliminary evaluation in a breast cancer context.

Vascular response patterns to targeted therapies in murine breast cancer models with divergent degrees of malignancy.

BACKGROUND: Response assessment of targeted cancer therapies is becoming increasingly challenging, as it is not adequately assessable with conventional morphological and volumetric analyses of tumor lesions. The tumor microenvironment is particularly constituted by tumor vasculature which is altered by various targeted therapies. The aim of this study was to noninvasively assess changes in tumor perfusion and vessel permeability after targeted therapy in murine models of breast cancer with divergent degrees of malignancy. METHODS: Low malignant 67NR or highly malignant 4T1 tumor-bearing mice were treated with either the multi-kinase inhibitor sorafenib or immune checkpoint inhibitors (ICI, combination of anti-PD1 and anti-CTLA4). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with i.v. injection of albumin-binding gadofosveset was conducted on a 9.4 T small animal MRI. Ex vivo validation of MRI results was achieved by transmission electron microscopy, immunohistochemistry and laser ablation-inductively coupled plasma-mass spectrometry. RESULTS: Therapy-induced changes in tumor vasculature differed between low and highly malignant tumors. Sorafenib treatment led to decreased tumor perfusion and endothelial permeability in low malignant 67NR tumors. In contrast, highly malignant 4T1 tumors demonstrated characteristics of a transient window of vascular normalization with an increase in tumor perfusion and permeability early after therapy initiation, followed by decreased perfusion and permeability parameters. In the low malignant 67NR model, ICI treatment also mediated vessel-stabilizing effects with decreased tumor perfusion and permeability, while ICI-treated 4T1 tumors exhibited increasing tumor perfusion with excessive vascular leakage. CONCLUSION: DCE-MRI enables noninvasive assessment of early changes in tumor vasculature after targeted therapies, revealing different response patterns between tumors with divergent degrees of malignancy. DCE-derived tumor perfusion and permeability parameters may serve as vascular biomarkers that allow for repetitive examination of response to antiangiogenic treatment or immunotherapy.

Low bone mineral density is a prognostic factor for elderly patients with HCC undergoing TACE: results from a multicenter study.

OBJECTIVES: Low bone mineral density (BMD) was recently identified as a novel risk factor for patients with hepatocellular carcinoma (HCC). In this multicenter study, we aimed to validate the role of BMD as a prognostic factor for patients with HCC undergoing transarterial chemoembolization (TACE). METHODS: This retrospective multicenter trial included 908 treatment-naïve patients with HCC who were undergoing TACE as a first-line treatment, at six tertiary care centers, between 2010 and 2020. BMD was assessed by measuring the mean Hounsfield units (HUs) in the midvertebral core of the 11th thoracic vertebra, on contrast-enhanced computer tomography performed before treatment. We assessed the influence of BMD on median overall survival (OS) and performed multivariate analysis including established estimates for survival. RESULTS: The median BMD was 145 HU (IQR, 115-175 HU). Patients with a high BMD (≥ 114 HU) had a median OS of 22.2 months, while patients with a low BMD (< 114 HU) had a lower median OS of only 16.2 months (p < .001). Besides albumin, bilirubin, tumor number, and tumor diameter, BMD remained an independent prognostic factor in multivariate analysis. CONCLUSIONS: BMD is an independent predictive factor for survival in elderly patients with HCC undergoing TACE. The integration of BMD into novel scoring systems could potentially improve survival prediction and clinical decision-making. KEY POINTS: • Bone mineral density can be easily assessed in routinely acquired pre-interventional computed tomography scans. • Bone mineral density is an independent predictive factor for survival in elderly patients with HCC undergoing TACE. • Thus, bone mineral density is a novel imaging biomarker for prognosis prediction in elderly patients with HCC undergoing TACE.

Multiparametric MRI enables for differentiation of different degrees of malignancy in two murine models of breast cancer.

Objective: The objective of this study was to non-invasively differentiate the degree of malignancy in two murine breast cancer models based on identification of distinct tissue characteristics in a metastatic and non-metastatic tumor model using a multiparametric Magnetic Resonance Imaging (MRI) approach. Methods: The highly metastatic 4T1 breast cancer model was compared to the non-metastatic 67NR model. Imaging was conducted on a 9.4 T small animal MRI. The protocol was used to characterize tumors regarding their structural composition, including heterogeneity, intratumoral edema and hemorrhage, as well as endothelial permeability using apparent diffusion coefficient (ADC), T1/T2 mapping and dynamic contrast-enhanced (DCE) imaging. Mice were assessed on either day three, six or nine, with an i.v. injection of the albumin-binding contrast agent gadofosveset. Ex vivo validation of the results was performed with laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), histology, immunhistochemistry and electron microscopy. Results: Significant differences in tumor composition were observed over time and between 4T1 and 67NR tumors. 4T1 tumors showed distorted blood vessels with a thin endothelial layer, resulting in a slower increase in signal intensity after injection of the contrast agent. Higher permeability was further reflected in higher Ktrans values, with consecutive retention of gadolinium in the tumor interstitium visible in MRI. 67NR tumors exhibited blood vessels with a thicker and more intact endothelial layer, resulting in higher peak enhancement, as well as higher maximum slope and area under the curve, but also a visible wash-out of the contrast agent and thus lower Ktrans values. A decreasing accumulation of gadolinium during tumor progression was also visible in both models in LA-ICP-MS. Tissue composition of 4T1 tumors was more heterogeneous, with intratumoral hemorrhage and necrosis and corresponding higher T1 and T2 relaxation times, while 67NR tumors mainly consisted of densely packed tumor cells. Histogram analysis of ADC showed higher values of mean ADC, histogram kurtosis, range and the 90th percentile (p90), as markers for the heterogenous structural composition of 4T1 tumors. Principal component analysis (PCA) discriminated well between the two tumor models. Conclusions: Multiparametric MRI as presented in this study enables for the estimation of malignant potential in the two studied tumor models via the assessment of certain tumor features over time.

Imaging standardisation in metastatic colorectal cancer: A joint EORTC-ESOI-ESGAR expert consensus recommendation.

BACKGROUND: Treatment monitoring in metastatic colorectal cancer (mCRC) relies on imaging to evaluate the tumour burden. Response Evaluation Criteria in Solid Tumors provide a framework on reporting and interpretation of imaging findings yet offer no guidance on a standardised imaging protocol tailored to patients with mCRC. Imaging protocol heterogeneity remains a challenge for the reproducibility of conventional imaging end-points and is an obstacle for research on novel imaging end-points. PATIENTS AND METHODS: Acknowledging the recently highlighted potential of radiomics and artificial intelligence tools as decision support for patient care in mCRC, a multidisciplinary, international and expert panel of imaging specialists was formed to find consensus on mCRC imaging protocols using the Delphi method. RESULTS: Under the guidance of the European Organisation for Research and Treatment of Cancer (EORTC) Imaging and Gastrointestinal Tract Cancer Groups, the European Society of Oncologic Imaging (ESOI) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the EORTC-ESOI-ESGAR core imaging protocol was identified. CONCLUSION: This consensus protocol attempts to promote standardisation and to diminish variations in patient preparation, scan acquisition and scan reconstruction. We anticipate that this standardisation will increase reproducibility of radiomics and artificial intelligence studies and serve as a catalyst for future research on imaging end-points. For ongoing and future mCRC trials, we encourage principal investigators to support the dissemination of these imaging standards across recruiting centres.

In vivo imaging of microenvironmental and anti-PD-L1-mediated dynamics in cancer using S100A8/S100A9 as an imaging biomarker.

PURPOSE: As a promotor of tumor invasion and tumor microenvironment (TME) formation, the protein complex S100A8/S100A9 is associated with poor prognosis. Our aim was to further evaluate its origin and regulatory effects, and to establish an imaging biomarker for TME activity. METHODS: S100A9-/-cells (ko) were created from syngeneic murine breast cancer 4T1 (high malignancy) and 67NR (low malignancy) wildtype (wt) cell lines and implanted into either female BALB/c wildtype or S100A9-/- mice (n = 10 each). Anti-S100A9-Cy5.5-targeted fluorescence reflectance imaging was performed at 0 h and 24 h after injection. Potential early changes of S100A9-presence under immune checkpoint inhibition (anti-PD-L1, n = 7 vs. rat IgG2b as isotype control, n = 3) were evaluated. RESULTS: In S100A9-/-mice contrast-to-noise-ratios were significantly reduced for wt and S100A9-/-tumors. No significant differences were detected for 4T1 ko and 67NR ko cells as compared to wildtype cells. Under anti-PD-L1 treatment S100A9 presence significantly decreased compared with the control group. CONCLUSION: Our results confirm a secretion of S100A8/S100A9 by the TME, while tumor cells do not apparently release the protein. Under immune checkpoint inhibition S100A9-imaging reports an early decrease of TME activity. Therefore, S100A9-specific imaging may serve as an imaging biomarker for TME formation and activity.

Tumor Burden in Patients With Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Head-to-Head Comparison of Current Scoring Systems.

Objectives: Recently, several scoring systems for prognosis prediction based on tumor burden have been promoted for patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). This multicenter study aimed to perform the first head-to-head comparison of three scoring systems. Methods: We retrospectively enrolled 849 treatment-naïve patients with HCC undergoing TACE at six tertiary care centers between 2010 and 2020. The tumor burden score (TBS), the Six-and-Twelve score (SAT), and the Seven-Eleven criteria (SEC) were calculated based on the maximum lesion size and the number of tumor nodes. All scores were compared in univariate and multivariate regression analyses, adjusted for established risk factors. Results: The median overall survival (OS) times were 33.0, 18.3, and 12.8 months for patients with low, medium, and high TBS, respectively (p<0.001). The median OS times were 30.0, 16.9, and 10.2 months for patients with low, medium, and high SAT, respectively (p<0.001). The median OS times were 27.0, 16.7, and 10.5 for patients with low, medium, and high SEC, respectively (p<0.001). In a multivariate analysis, only the SAT remained an independent prognostic factor. The C-Indexes were 0.54 for the TBS, 0.59 for the SAT, and 0.58 for the SEC. Conclusion: In a direct head-to-head comparison, the SAT was superior to the TBS and SEC in survival stratification and predictive ability. Therefore, the SAT can be considered when estimating the tumor burden. However, all three scores showed only moderate predictive power. Therefore, tumor burden should only be one component among many in treatment decision making.

[Mediastinal lesions : The most common pathologies in chest X-rays and their correlations in computed tomography]. / Mediastinale Läsionen : Die häufigsten Pathologien in der Röntgenaufnahme des Thorax und deren Korrelation in der Computertomographie.

BACKGROUND: Many pathologies of the mediastinum can be diagnosed using standard radiographs. Correlation of radiographic findings with computed tomography (CT) is instructive for a better understanding and can help improve detection rates of mediastinal lesions. OBJECTIVES: To identify the most common mediastinal lesions and to correlate their features in chest radiographs and CT. METHODS: The International Thymic Malignancy Interest Group (ITMIG) classification in the anterior, middle, and posterior mediastinum is based on anatomic landmarks. Used as a tool to characterize mediastinal lesions this classification is applied in this article. RESULTS: The most common lesions include mediastinal goiter, germ cell and thymic neoplasms in the anterior mediastinum, lymphadenopathy in the middle mediastinum, and neurogenic neoplasms in the posterior mediastinum. Other lesions of neoplastic or non-neoplastic origin can be distinguished in the three compartments and should be considered in the differential diagnosis. CONCLUSIONS: Knowledge of the most common pathologies in the three mediastinal compartments can accelerate differential diagnosis. Understanding the normal mediastinal lines is key in anatomic localization and detection of many lesions in chest radiographs.

[Complete response after neoadjuvant therapy: how certain is radiology?] / Komplette Response nach neoadjuvanter Therapie: Wie sicher ist die Radiologie?

The concept of total neoadjuvant therapy (TNT) means a paradigm shift in the treatment of patients with rectal cancer. In cases in which the TNT induced a complete clinical response (cCR), an organ preserving watch and wait therapy concept can now be provided more often; however, this increases the demand for imaging for the determination of cCR and in the subsequent follow-up. In this article, the performance of radiology in these scenarios will be evaluated and discussed. Magnetic resonance imaging (MRI) is the current standard for local assessment of the rectum with a high sensitivity for diagnosis and staging of rectal cancer, residual tumor and tumor recurrence. However, the certain exclusion of residual malignant tissue is still difficult, in particular the differentiation of residual scar tissue from vital residual tumor is only possible with low specificity and a moderate negative predictive value (NPV). The currently discussed criteria for the assessment of imaging have not yet been validated in large cohorts and are frequently subjective. An improvement of the diagnostic accuracy for identification of cCR in patients after TNT and for monitoring patients in watch and wait treatment concepts can certainly be achieved by the integration of MRI, endoscopy and endosonography as well as clinical parameters. This should enable for identification of patients with an incomplete response or local recurrence, in time for extended treatment to be initiated without relevant impact on the patient outcome.

How Different Albumin-Binders Drive Probe Distribution of Fluorescent RGD Mimetics.

The biodistribution of medical imaging probes depends on the chemical nature of the probe and the preferred metabolization and excretion routes. Especially targeted probes, which have to reach a certain (sub)cellular destination, have to be guided to the tissue of interest. Therefore, small molecular probes need to exhibit a well-balanced polarity and lipophilicity to maintain an advantageous bioavailability. Labelled antibodies circulate for several days due to their size. To alter the biodistribution behavior of probes, different strategies have been pursued, including utilizing serum albumin as an inherent transport mechanism for small molecules. We describe here the modification of an existing fluorescent RGD mimetic probe targeted to integrin αvß3 with three different albumin binding moieties (ABMs): a diphenylcyclohexyl (DPCH) group, a p-iodophenyl butyric acid (IPBA) and a fatty acid (FA) group with the purpose to identify an optimal ABM for molecular imaging applications. All three modifications result in transient albumin binding and a preservation of the target binding capability. Spectrophotometric measurements applying variable amounts of bovine serum albumin (BSA) reveal considerable differences between the compounds concerning their absorption and emission characteristics and hence their BSA binding mode. In vivo the modified probes were investigated in a murine U87MG glioblastoma xenograft model over the course of 1 wk by fluorescence reflectance imaging (FRI) and fluorescence mediated tomography (FMT). While the unmodified probe was excreted rapidly, the albumin-binding probes were accumulating in tumor tissue for at least 5 days. Considerable differences between the three probes in biodistribution and excretion characteristics were proved, with the DPCH-modified probe showing the highest overall signal intensities, while the FA-modified probe exhibits a low but more specific fluorescent signal. In conclusion, the modification of small molecular RGD mimetics with ABMs can precisely fine-tune probe distribution and offers potential for future clinical applications.

Tumor-Associated Macrophages-Implications for Molecular Oncology and Imaging.

Tumor-associated macrophages (TAMs) represent the largest group of leukocytes within the tumor microenvironment (TME) of solid tumors and orchestrate the composition of anti- as well as pro-tumorigenic factors. This makes TAMs an excellent target for novel cancer therapies. The plasticity of TAMs resulting in varying membrane receptors and expression of intracellular proteins allow the specific characterization of different subsets of TAMs. Those markers similarly allow tracking of TAMs by different means of molecular imaging. This review aims to provides an overview of the origin of tumor-associated macrophages, their polarization in different subtypes, and how characteristic markers of the subtypes can be used as targets for molecular imaging and theranostic approaches.

Molecular Imaging of Immunity and Inflammation and Its Impact on Precision Medicine.

Biomedical research has, over the past decades, found components of the immune system at the functional center of almost every pathophysiological condition and disease [...].

S100A9-Imaging Enables Estimation of Early Therapy-Mediated Changes in the Inflammatory Tumor Microenvironment.

(1) Background: The prognosis of cancer is dependent on immune cells in the tumor microenvironment (TME). The protein S100A9 is an essential regulator of the TME, associated with poor prognosis. In this study, we evaluated early therapy effects on the TME in syngeneic murine breast cancer via S100A9-specific in vivo imaging. (2) Methods: Murine 4T1 cells were implanted orthotopically in female BALB/c mice (n = 59). Tumor size-adapted fluorescence imaging was performed before and 5 days after chemo- (Doxorubicin, n = 20), anti-angiogenic therapy (Bevacizumab, n = 20), or placebo (NaCl, n = 19). Imaging results were validated ex vivo (immunohistochemistry, flow cytometry). (3) Results: While tumor growth revealed no differences (p = 0.48), fluorescence intensities (FI) for S100A9 in Bevacizumab-treated tumors were significantly lower as compared to Doxorubicin (2.60 vs. 15.65 AU, p < 0.0001). FI for Doxorubicin were significantly higher compared to placebo (8.95 AU, p = 0.01). Flow cytometry revealed shifts in monocytic and T-cell cell infiltrates under therapy, correlating with imaging. (4) Conclusions: S100A9-specific imaging enables early detection of therapy effects visualizing immune cell activity in the TME, even before clinically detectable changes in tumor size. Therefore, it may serve as a non-invasive imaging biomarker for early therapy effects.