Multiparametric Magnetic Resonance Imaging for Immediate Target Hit Assessment of CD13—Targeted Tissue Factor tTF-NGR in Advanced Malignant Disease
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...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-11-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/23/5880 |
| _version_ | 1797507974187450368 |
|---|---|
| author | Mirjam Gerwing Tobias Krähling Christoph Schliemann Saliha Harrach Christian Schwöppe Andrew F. Berdel Sebastian Klein Wolfgang Hartmann Eva Wardelmann Walter L. Heindel Georg Lenz Wolfgang E. Berdel Moritz Wildgruber |
| author_facet | Mirjam Gerwing Tobias Krähling Christoph Schliemann Saliha Harrach Christian Schwöppe Andrew F. Berdel Sebastian Klein Wolfgang Hartmann Eva Wardelmann Walter L. Heindel Georg Lenz Wolfgang E. Berdel Moritz Wildgruber |
| author_sort | Mirjam Gerwing |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T04:56:01Z |
| format | Article |
| id | doaj.art-3b1ca046d01d481cad1efb3ad00ca63f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T04:56:01Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-3b1ca046d01d481cad1efb3ad00ca63f2023-11-23T02:10:44ZengMDPI AGCancers2072-66942021-11-011323588010.3390/cancers13235880Multiparametric Magnetic Resonance Imaging for Immediate Target Hit Assessment of CD13—Targeted Tissue Factor tTF-NGR in Advanced Malignant DiseaseMirjam Gerwing0Tobias Krähling1Christoph Schliemann2Saliha Harrach3Christian Schwöppe4Andrew F. Berdel5Sebastian Klein6Wolfgang Hartmann7Eva Wardelmann8Walter L. Heindel9Georg Lenz10Wolfgang E. Berdel11Moritz Wildgruber12Clinic of Radiology, University Hospital Muenster, D-48149 Muenster, GermanyClinic of Radiology, University Hospital Muenster, D-48149 Muenster, GermanyDepartment of Medicine A, Hematology, Hemostaseology, Oncology and Pulmonology, University Hospital Muenster, D-48149 Muenster, GermanyDepartment of Medicine A, Hematology, Hemostaseology, Oncology and Pulmonology, University Hospital Muenster, D-48149 Muenster, GermanyDepartment of Medicine A, Hematology, Hemostaseology, Oncology and Pulmonology, University Hospital Muenster, D-48149 Muenster, GermanyDepartment of Medicine A, Hematology, Hemostaseology, Oncology and Pulmonology, University Hospital Muenster, D-48149 Muenster, GermanyGerhard-Domagk-Institute for Pathology, University of Muenster, D-48149 Muenster, GermanyGerhard-Domagk-Institute for Pathology, University of Muenster, D-48149 Muenster, GermanyGerhard-Domagk-Institute for Pathology, University of Muenster, D-48149 Muenster, GermanyClinic of Radiology, University Hospital Muenster, D-48149 Muenster, GermanyDepartment of Medicine A, Hematology, Hemostaseology, Oncology and Pulmonology, University Hospital Muenster, D-48149 Muenster, GermanyDepartment of Medicine A, Hematology, Hemostaseology, Oncology and Pulmonology, University Hospital Muenster, D-48149 Muenster, GermanyClinic of Radiology, University Hospital Muenster, D-48149 Muenster, GermanyEarly 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.https://www.mdpi.com/2072-6694/13/23/5880dynamic contrast-enhanced MRIvascular volume fractionapparent diffusion coefficienttTF-NGRvascular targeting |
| spellingShingle | Mirjam Gerwing Tobias Krähling Christoph Schliemann Saliha Harrach Christian Schwöppe Andrew F. Berdel Sebastian Klein Wolfgang Hartmann Eva Wardelmann Walter L. Heindel Georg Lenz Wolfgang E. Berdel Moritz Wildgruber Multiparametric Magnetic Resonance Imaging for Immediate Target Hit Assessment of CD13—Targeted Tissue Factor tTF-NGR in Advanced Malignant Disease Cancers dynamic contrast-enhanced MRI vascular volume fraction apparent diffusion coefficient tTF-NGR vascular targeting |
| title | Multiparametric Magnetic Resonance Imaging for Immediate Target Hit Assessment of CD13—Targeted Tissue Factor tTF-NGR in Advanced Malignant Disease |
| title_full | Multiparametric Magnetic Resonance Imaging for Immediate Target Hit Assessment of CD13—Targeted Tissue Factor tTF-NGR in Advanced Malignant Disease |
| title_fullStr | Multiparametric Magnetic Resonance Imaging for Immediate Target Hit Assessment of CD13—Targeted Tissue Factor tTF-NGR in Advanced Malignant Disease |
| title_full_unstemmed | Multiparametric Magnetic Resonance Imaging for Immediate Target Hit Assessment of CD13—Targeted Tissue Factor tTF-NGR in Advanced Malignant Disease |
| title_short | Multiparametric Magnetic Resonance Imaging for Immediate Target Hit Assessment of CD13—Targeted Tissue Factor tTF-NGR in Advanced Malignant Disease |
| title_sort | multiparametric magnetic resonance imaging for immediate target hit assessment of cd13 targeted tissue factor ttf ngr in advanced malignant disease |
| topic | dynamic contrast-enhanced MRI vascular volume fraction apparent diffusion coefficient tTF-NGR vascular targeting |
| url | https://www.mdpi.com/2072-6694/13/23/5880 |
| work_keys_str_mv | AT mirjamgerwing multiparametricmagneticresonanceimagingforimmediatetargethitassessmentofcd13targetedtissuefactorttfngrinadvancedmalignantdisease AT tobiaskrahling multiparametricmagneticresonanceimagingforimmediatetargethitassessmentofcd13targetedtissuefactorttfngrinadvancedmalignantdisease AT christophschliemann multiparametricmagneticresonanceimagingforimmediatetargethitassessmentofcd13targetedtissuefactorttfngrinadvancedmalignantdisease AT salihaharrach multiparametricmagneticresonanceimagingforimmediatetargethitassessmentofcd13targetedtissuefactorttfngrinadvancedmalignantdisease AT christianschwoppe multiparametricmagneticresonanceimagingforimmediatetargethitassessmentofcd13targetedtissuefactorttfngrinadvancedmalignantdisease AT andrewfberdel multiparametricmagneticresonanceimagingforimmediatetargethitassessmentofcd13targetedtissuefactorttfngrinadvancedmalignantdisease AT sebastianklein multiparametricmagneticresonanceimagingforimmediatetargethitassessmentofcd13targetedtissuefactorttfngrinadvancedmalignantdisease AT wolfganghartmann multiparametricmagneticresonanceimagingforimmediatetargethitassessmentofcd13targetedtissuefactorttfngrinadvancedmalignantdisease AT evawardelmann multiparametricmagneticresonanceimagingforimmediatetargethitassessmentofcd13targetedtissuefactorttfngrinadvancedmalignantdisease AT walterlheindel multiparametricmagneticresonanceimagingforimmediatetargethitassessmentofcd13targetedtissuefactorttfngrinadvancedmalignantdisease AT georglenz multiparametricmagneticresonanceimagingforimmediatetargethitassessmentofcd13targetedtissuefactorttfngrinadvancedmalignantdisease AT wolfgangeberdel multiparametricmagneticresonanceimagingforimmediatetargethitassessmentofcd13targetedtissuefactorttfngrinadvancedmalignantdisease AT moritzwildgruber multiparametricmagneticresonanceimagingforimmediatetargethitassessmentofcd13targetedtissuefactorttfngrinadvancedmalignantdisease |