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Published on: February 17, 2022
Multiparametric Magnetic Resonance Imaging for Immediate Target Hit Assessment of CD13-Targeted Tissue Factor tTF-NGR
Mirjam Gerwing1, Tobias Krähling1, Christoph Schliemann2
1Clinic of Radiology, University Hospital Muenster, D-48149 Muenster, Germany.
Abstract:
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.
Insights
Early assessment of anti-cancer therapy effectiveness is crucial. Multiparametric MRI revealed that CD13-targeted tissue factor (tTF-NGR) therapy rapidly reduces tumor perfusion, indicating an early target hit in advanced cancers.
Area of Science:
- Oncologic Imaging
- Medical Oncology
- Radiology
Background:
- Early assessment of anti-cancer therapy efficacy is vital for patient management.
- CD13-targeted tissue factor (tTF-NGR) is a novel agent for advanced malignant diseases.
Purpose of the Study:
- To assess the immediate target hit and effectiveness of tTF-NGR using multiparametric MRI.
- To evaluate early changes in tumor perfusion and vascularity following tTF-NGR administration.
Main Methods:
- A phase I trial involving 17 patients with advanced solid malignancies.
- Multiparametric MRI including diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) imaging, and vascular volume fraction (VVF) assessment.
- Imaging was performed before therapy, 5 hours after the first infusion, and after 5 days.
Main Results:
- DCE and VVF values decreased within 5 hours, indicating early target hit and reduced tumor perfusion due to tTF-NGR.
- Simultaneously, apparent diffusion coefficient (ADC) values increased post-infusion.
- Reversed imaging changes were observed in patients who required anticoagulation due to adverse events.
Conclusions:
- Multiparametric MRI enables early assessment of target hit within 5 hours of tTF-NGR initiation.
- This imaging approach can evaluate changes in tumor perfusion during vessel-occluding therapy.
- Early detection of treatment response or adverse effects is possible with this protocol.
