scholarly journals Multiparametric Magnetic Resonance Imaging for Immediate Target Hit Assessment of CD13—Targeted Tissue Factor tTF-NGR in Advanced Malignant Disease

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5880
Author(s):  
Mirjam Gerwing ◽  
Tobias Krähling ◽  
Christoph Schliemann ◽  
Saliha Harrach ◽  
Christian Schwöppe ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Malignant Disease ◽  
Volume Fraction ◽  
Multiparametric Mri ◽  
Tumor Perfusion ◽  
Tumor Vessel ◽  
Early Assessment ◽  
Imaging Protocol ◽  
Therapy Initiation ◽  
Adc Values

Early assessment of target hit in anti-cancer therapies is a major task in oncologic imaging. In this study, immediate target hit and effectiveness of CD13-targeted tissue factor tTF-NGR in patients with advanced malignant disease enrolled in a phase I trial was assessed using a multiparametric MRI protocol. Seventeen patients with advanced solid malignancies were enrolled in the trial and received tTF-NGR for at least one cycle of five daily infusions. Tumor target lesions were imaged with multiparametric MRI before therapy initiation, five hours after the first infusion and after five days. The imaging protocol comprised ADC, calculated from DWI, and DCE imaging and vascular volume fraction (VVF) assessment. DCE and VVF values decreased within 5 h after therapy initiation, indicating early target hit with a subsequent decrease in tumor perfusion due to selective tumor vessel occlusion and thrombosis induced by tTF-NGR. Simultaneously, ADC values increased at five hours after tTF-NGR administration. In four patients, treatment had to be stopped due to an increase in troponin T hs, with subsequent anticoagulation. In these patients, a reversed effect, with DCE and VVF values increasing and ADC values decreasing, was observed after anticoagulation. Changes in imaging parameters were independent of the mean vessel density determined by immunohistochemistry. By using a multiparametric imaging approach, changes in tumor perfusion after initiation of a tumor vessel occluding therapy can be evaluated as early as five hours after therapy initiation, enabling early assessment of target hit.

scholarly journals Differentiating Glioblastomas from Solitary Brain Metastases: An Update on the Current Literature of Advanced Imaging Modalities

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2960
Author(s):  
Austin-John Fordham ◽  
Caitlin-Craft Hacherl ◽  
Neal Patel ◽  
Keri Jones ◽  
Brandon Myers ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Brain Metastases ◽  
Clinical Assessment ◽  
Volume Fraction ◽  
Imaging Modalities ◽  
Current Evidence ◽  
Dynamic Susceptibility ◽  
Advanced Imaging ◽  
Imaging Protocol ◽  
Solitary Brain Metastases

Differentiating between glioblastomas and solitary brain metastases proves to be a challenging diagnosis for neuroradiologists, as both present with imaging patterns consisting of peritumoral hyperintensities with similar intratumoral texture on traditional magnetic resonance imaging sequences. Early diagnosis is paramount, as each pathology has completely different methods of clinical assessment. In the past decade, recent developments in advanced imaging modalities enabled providers to acquire a more accurate diagnosis earlier in the patient’s clinical assessment, thus optimizing clinical outcome. Dynamic susceptibility contrast has been optimized for detecting relative cerebral blood flow and relative cerebral blood volume. Diffusion tensor imaging can be used to detect changes in mean diffusivity. Neurite orientation dispersion and density imaging is an innovative modality detecting changes in intracellular volume fraction, isotropic volume fraction, and extracellular volume fraction. Magnetic resonance spectroscopy is able to assist by providing a metabolic descriptor while detecting variable ratios of choline/N-acetylaspartate, choline/creatine, and N-acetylaspartate/creatine. Finally, radiomics and machine learning algorithms have been devised to assist in improving diagnostic accuracy while often utilizing more than one advanced imaging protocol per patient. In this review, we provide an update on all the current evidence regarding the identification and differentiation of glioblastomas from solitary brain metastases.

scholarly journals NG2 proteoglycan as a pericyte target for anticancer therapy by tumor vessel infarction with retargeted tissue factor

Oncotarget ◽  
2016 ◽  
Vol 7 (6) ◽  
pp. 6774-6789 ◽  
Author(s):  
Caroline Brand ◽  
Christoph Schliemann ◽  
Janine Ring ◽  
Torsten Kessler ◽  
Sebastian Bäumer ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Anticancer Therapy ◽  
Tumor Vessel ◽  
Ng2 Proteoglycan

scholarly journals Assessment of the percentage of apparent diffusion coefficient value changes as an early indicator of the response of colorectal hepatic metastases to chemotherapy

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Nada Gamal El-Husseiny ◽  
Sayed Mohamed Mehana ◽  
Sherif Farouk El Zawawy
Keyword(s):  
Colorectal Cancer ◽  
Diffusion Coefficient ◽  
Apparent Diffusion Coefficient ◽  
Hepatic Metastasis ◽  
Percentage Increase ◽  
Early Assessment ◽  
Response To Chemotherapy ◽  
Significant Difference ◽  
Apparent Diffusion ◽  
Adc Values

Abstract Background Colorectal cancer is considered one of the most common causes of cancer-related deaths worldwide. We aim to evaluate the efficacy of DWI-MRI in predicting response to chemotherapy in this cohort. The study included 30 lesions in 20 biopsy proven-colorectal cancer patients with hepatic metastasis larger than 1 cm. All patients underwent both triphasic CT with intravenous contrast, pre-chemotherapy MRI (axial T2 and DW sequences) which was repeated 21 days following chemotherapy. A follow-up CT was done 2 months later. The response of the lesions was evaluated using the RESCIST criteria. On MRI, the lesions corresponding to the ones chosen on CT were identified and the apparent diffusion coefficient (ADC) values of pre- and post-chemotherapy images were recorded and correlated with the CT results. Results In the study, 17 (56.7%) of the lesions showed response to chemotherapy while 13 (43.3%) were non-responding. There was no significant difference in pretreatment ADC values between responding and non-responding lesions (p = 0.14). The mean percentage increase in ADC values in responding lesions was 42% compared to 18% in non-responding lesions (p < 0.001). Lesions that showed less than 18% increase were all found to be non-responsive Conclusion DWI-MRI has an emerging role in early assessment of early treatment response that can be detected before morphological response for patients with hepatic metastasis from colorectal cancer. Based on our study, the use of 25 % as the cutoff point of percent difference in ADC for detection of non-responding lesions proved to be successful only 21 days after the 1st chemotherapy cycle.

Lipoprotein Associated Coagulation Inhibitor, Factor VII, Antithrombin III, and Monocyte Tissue Factor Following Surgery

1991 ◽  
Vol 66 (05) ◽  
pp. 534-539 ◽  
Author(s):  
Steven D Carson ◽  
William D Haire ◽  
George J Broze ◽  
William F Novotny ◽  
Samuel J Pirrucello ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Malignant Disease ◽  
Antithrombin Iii ◽  
Peripheral Blood Monocyte ◽  
Factor Vii ◽  
Normal Ranges ◽  
At Iii ◽  
Coagulation Inhibitor ◽  
Temporal Occurrence ◽  
Diagnosis Of Infection

SummaryFifteen patients undergoing major surgical procedures were evaluated for lipoprotein associated coagulation inhibitor (LACI) antigen, factor VII (F VII), antithrombin III (AT III), and peripheral blood monocyte tissue factor (TF) activity immediately before surgery and on following days. A peak in monocyte TF activity occurred between the first and fifth days after surgery in 10 of the patients, while LACI, F VII, and AT III levels dropped in a qualitatively parallel manner in 8 of these patients. LACI, F VII, and AT III levels decreased after surgery in two additional patients even though TF activity also decreased after surgery in these patients. In the remaining 3 patients who developed infections during the study, TF activity rose within 2 days of the diagnosis of infection in addition to the postoperative peak. In two of these patients, LACI levels increased dramatically near the end of the study period without concomitant changes in F VII and AT III. Overall, the presurgical TF levels in disrupted monocytes varied 52-fold and the maximal TF activity varied 24-fold among patients. The TF response following surgery is therefore heterogenous in both temporal occurrence and magnitude of the postsurgical peak. The patients also varied considerably in the presurgical levels of monocyte TF activity. A possible association between the level of presurgical TF activity and the magnitude of the postsurgical peak was noted. Thirteen of the patients had malignant disease, and, as a group, had presurgical levels of LACI (83 ± 26; mean ± SD), F VII (124 ± 22) and AT III (111 ± 14) within the normal ranges established with pooled reference plasma and similar values for three normal donors studied over the same period (AT III 121 ± 6, LACI 95 ± 4, and F VII 112 ± 29). No cause-effect relationship could be established between changes in TF activity and changes in the other factors measured. Patient- or therapy-specific variables may determine postoperative variations in LACI, F VII, AT III, and monocyte TF.

scholarly journals Diagnostic value of diffusion-weighted imaging with synthetic b-values in breast tumors: comparison with dynamic contrast-enhanced and multiparametric MRI

2020 ◽  
Vol 31 (1) ◽  
pp. 356-367
Author(s):  
Isaac Daimiel Naranjo ◽  
Roberto Lo Gullo ◽  
Carolina Saccarelli ◽  
Sunitha B. Thakur ◽  
Almir Bitencourt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Image Quality ◽  
Cancer Detection ◽  
Multiparametric Mri ◽  
Breast Cancer Detection ◽  
Dense Breast ◽  
B Values ◽  
Dce Mri ◽  
Adc Values ◽  
Lesion Conspicuity

Abstract Objectives To assess DWI for tumor visibility and breast cancer detection by the addition of different synthetic b-values. Methods Eighty-four consecutive women who underwent a breast-multiparametric-MRI (mpMRI) with enhancing lesions on DCE-MRI (BI-RADS 2–5) were included in this IRB-approved retrospective study from September 2018 to March 2019. Three readers evaluated DW acquired b-800 and synthetic b-1000, b-1200, b-1500, and b-1800 s/mm2 images for lesion visibility and preferred b-value based on lesion conspicuity. Image quality (1–3 scores) and breast composition (BI-RADS) were also recorded. Diagnostic parameters for DWI were determined using a 1–5 malignancy score based on qualitative imaging parameters (acquired + preferred synthetic b-values) and ADC values. BI-RADS classification was used for DCE-MRI and quantitative ADC values + BI-RADS were used for mpMRI. Results Sixty-four malignant (average = 23 mm) and 39 benign (average = 8 mm) lesions were found in 80 women. Although b-800 achieved the best image quality score, synthetic b-values 1200–1500 s/mm2 were preferred for lesion conspicuity, especially in dense breast. b-800 and synthetic b-1000/b-1200 s/mm2 values allowed the visualization of 84–90% of cancers visible with DCE-MRI performing better than b-1500/b-1800 s/mm2. DWI was more specific (86.3% vs 65.7%, p < 0.001) but less sensitive (62.8% vs 90%, p < 0.001) and accurate (71% vs 80.7%, p = 0.003) than DCE-MRI for breast cancer detection, where mpMRI was the most accurate modality accounting for less false positive cases. Conclusion The addition of synthetic b-values enhances tumor conspicuity and could potentially improve tumor visualization particularly in dense breast. However, its supportive role for DWI breast cancer detection is still not definite. Key Points • The addition of synthetic b-values (1200–1500 s/mm2) to acquired DWI afforded a better lesion conspicuity without increasing acquisition time and was particularly useful in dense breasts. • Despite the use of synthetic b-values, DWI was less sensitive and accurate than DCE-MRI for breast cancer detection. • A multiparametric MRI modality still remains the best approach having the highest accuracy for breast cancer detection and thus reducing the number of unnecessary biopsies.

Low-Energy Ultrasound Treatment Improves Regional Tumor Vessel Infarction by Retargeted Tissue Factor

2015 ◽  
Vol 34 (7) ◽  
pp. 1227-1236 ◽  
Author(s):  
Caroline Brand ◽  
Stefanie Dencks ◽  
Georg Schmitz ◽  
Mareike Mühlmeister ◽  
Jörg Stypmann ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Low Energy ◽  
Ultrasound Treatment ◽  
Tumor Vessel

Infarction of tumor vessels by NGR-peptide–directed targeting of tissue factor: experimental results and first-in-man experience

Blood ◽  
2009 ◽  
Vol 113 (20) ◽  
pp. 5019-5027 ◽  
Author(s):  
Ralf Bieker ◽  
Torsten Kessler ◽  
Christian Schwöppe ◽  
Teresa Padró ◽  
Thorsten Persigehl ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Tissue Factor ◽  
Solid Tumors ◽  
Xenograft Model ◽  
Coagulation Factor ◽  
In Vivo Studies ◽  
Tumor Perfusion ◽  
Good Tolerability ◽  
Tumor Vessels ◽  
Ngr Peptide

Abstract We induced thrombosis of blood vessels in solid tumors in mice by a fusion protein consisting of the extracellular domain of tissue factor (truncated tissue factor, tTF) and the peptide GNGRAHA, targeting aminopeptidase N (CD13) and the integrin αvβ3 (CD51/CD61) on tumor vascular endothelium. The designed fusion protein tTF-NGR retained its thrombogenic activity as demonstrated by coagulation assays. In vivo studies in mice bearing established human adenocarcinoma (A549), melanoma (M21), and fibrosarcoma (HT1080) revealed that systemic administration of tTF-NGR induced partial or complete thrombotic occlusion of tumor vessels as shown by histologic analysis. tTF-NGR, but not untargeted tTF, induced significant tumor growth retardation or regression in all 3 types of solid tumors. Thrombosis induction in tumor vessels by tTF-NGR was also shown by contrast enhanced magnetic resonance imaging (MRI). In the human fibrosarcoma xenograft model, MRI revealed a significant reduction of tumor perfusion by administration of tTF-NGR. Clinical first-in-man application of low dosages of this targeted coagulation factor revealed good tolerability and decreased tumor perfusion as measured by MRI. Targeted thrombosis in the tumor vasculature induced by tTF-NGR may be a promising strategy for the treatment of cancer.

scholarly journals Multiparametric MRI with diffusion-weighted imaging in predicting response to chemotherapy in cases of osteosarcoma and Ewing’s sarcoma

2020 ◽  
Vol 93 (1115) ◽  
pp. 20200257
Author(s):  
Mahmoud Mohamed Saleh ◽  
Tamer Moustafa Abdelrahman ◽  
Youusef Madney ◽  
Ghada Mohamed ◽  
Ahmed Mohammed Shokry ◽  
...  
Keyword(s):  
Diffusion Weighted Imaging ◽  
Tumor Volume ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Multiparametric Mri ◽  
Dce Mri ◽  
Recist 1.1 ◽  
Progressive Group ◽  
Adc Values ◽  
Modified Recist

Objective: To evaluate the multiparametric MRI in predicting chemotherapy response in pathologically proven cases of osteosarcoma and Ewing’s sarcoma. Correlation between the tumor size changes and internal breakdown using RECIST 1.1, modified RECIST, quantitative apparent diffusion coefficient (ADC) and tumor volume as well as dynamic contrast-enhanced MRI (DCE-MRI). Methods: The study included 104 patients pathologically proved osteosarcoma (53) and Ewing`s sarcoma (51) underwent MRI examinations; before and after chemotherapy. All patients were assessed using the RECIST 1.1 criteria, m-RECIST, quantitative ADC, and tumor volume evaluation. 21 patients underwent DCE-MRI curve type with quantitative parameters. Correlation between the different evaluations was carried out. Results were correlated with the post-operative pathology in 42 patients who underwent surgery and for statistical evaluation, Those patients were classified into responders (≥90% necrosis) and non-responders (<90% necrosis). Results: The initial mean ADC of 104 patients of osteosarcoma and Ewing’s sarcoma (0.90 ± 0.29) and (0.71 ± 0.16) respectively, differed significantly from that after treatment (1.62 ± 0.46) and (1.6 ± 0.39) respectively with (p<0.001). ADC variations (ADC%) in the non-progressive group were higher than those of the progressive group (128.3 ± 63.49 vs 36.34 ± 78.7) % with (p<0.001). ADC values and ADC variations were inversely correlated with morphologic changes, regardless of the effectiveness of chemotherapy expressed as changes in tumor size based on (RECIST 1.1, RECIST, and 3D volume). Linear regression analysis revealed a Pearson correlation coefficient of r=-0.427, -0.498 and -0.408, respectively with (p<0.001). An increase in the ADC value was not always associated with a reduction in tumor volume. The disease control rate (defined as the percentage of CR+PR+SD patients) was 89.4% and 93.9% according to RECIST 1.1 and m-RECIST respectively. 42 out of the 104 patients had postsurgical histological evaluation as regards the chemotherapeutic response divided into two groups. ADC values showed a statistically significant difference between Group A and Group B being more evident with minimum ADC% (p<0.001). Conclusion: Quantitative diffusion-weighted imaging with ADC mapping and ADC % after chemotherapy allows a detailed analysis of the treatment response in osteosarcoma and Ewing’s sarcoma. The therapeutic response can be underestimated using RECIST 1.1, so the modified RECIST should be also considered. Advances in knowledge: Quantitative ADC especially ADC% provided an accurate non-invasive tool in the assessment of post-therapeutic cases of osteosarcoma and Ewing's sarcoma

Non-invasive monitoring of tumor-vessel infarction by retargeted truncated tissue factor tTF–NGR using multi-modal imaging

Angiogenesis ◽  
2013 ◽  
Vol 17 (1) ◽  
pp. 235-246 ◽  
Author(s):  
Thorsten Persigehl ◽  
Janine Ring ◽  
Christoph Bremer ◽  
Walter Heindel ◽  
Richard Holtmeier ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Invasive Monitoring ◽  
Tumor Vessel ◽  
Non Invasive

scholarly journals NIMG-34. QUANTITATIVE MR PARAMETERS FOR THE PREDICTION OF EGFR AMPLIFICATION AND THE TERT PROMOTER MUTATION STATUS OF IDH-WILDTYPE LOWER-GRADE GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii155-ii155
Author(s):  
Yae Won Park ◽  
Sung Soo Ahn ◽  
Eui Hyun Kim ◽  
Seok-Gu Kang ◽  
Jong Hee Chang ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Volume Fraction ◽  
Independent Predictor ◽  
Extracellular Volume ◽  
Lower Grade ◽  
Dynamic Susceptibility ◽  
Multivariate Logistic Regression ◽  
Mutation Status ◽  
Egfr Amplification ◽  
Adc Values

Abstract OBJECTIVES To assess the predictive role of quantitative MRI parameters from DTI, dynamic susceptibility contrast (DSC), and dynamic contrast-enhanced (DCE) imaging in determining the epidermal growth factor receptor (EGFR) amplification and telomerase reverse transcriptase promoter (TERTp) mutation status of isocitrate dehydrogenase-wildtype (IDHwt) lower-grade gliomas (LGGs). METHODS A total of 49 patients with IDHwt LGGs with either known EGFR amplification (39 EGFR non-amplified, 10 EGFR-amplified) or TERTp mutation (19 TERTp wildtype, 21 TERTp mutant) statuses underwent preoperative MRI. The mean apparent diffusion coefficient (ADC), fractional anisotropy (FA), normalized cerebral blood volume (nCBV), normalized cerebral blood flow (nCBF), volume transfer constant (Ktrans), rate transfer coefficient (Kep), extravascular extracellular volume fraction (Ve), and plasma volume fraction (Vp) values were assessed. Univariate and multivariate logistic regression models were constructed to predict EGFR amplification and TERTp status. RESULTS EGFR-amplified tumors showed lower mean ADC values than EGFR non-amplified tumors (p = 0.019). Mean ADC was an independent predictor of EGFR amplification, with an AUC of 0.75. TERTp mutant tumors showed higher mean nCBV (p = 0.020), higher mean nCBF (p = 0.017), and higher mean Vp (p = 0.002) than TERTp wildtype tumors. With multivariate logistic regression, mean Vp was the only independent predictor of TERTp mutation status, with an AUC of 0.85. CONCLUSION Lower ADC values may be a useful marker for the prediction of EGFR amplification, whereas higher Vp values may be a useful marker for the prediction of the TERTp mutation status of IDHwt LGGs.

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