Monitoring antivascular therapy in head and neck cancer xenografts using contrast-enhanced MR and US imaging
Mukund Seshadri1, Nuno T Sacadura, Tonya Coulthard
1Department of Pharmacology and Therapeutics, Preclinical Imaging Laboratory, Roswell Park Cancer Institute, Buffalo, NY, USA. Mukund.Seshadri@roswellpark.org
Background:
The overall goal of this study was to non-invasively monitor changes in blood flow of squamous cell carcinoma of the head and neck (SCCHN) xenografts using contrast-enhanced magnetic resonance (MR) and ultrasound (US) imaging.
Methods:
Experimental studies were performed on mice bearing FaDu tumors and SCCHN xenografts derived from human surgical tissue. MR examinations were performed using gadofosveset trisodium at 4.7T. Change in T1-relaxation rate of tumors (ΔR1) and tumor enhancement parameters (amplitude, area under the curve-AUC) were measured at baseline and 24 h after treatment with a tumor-vascular disrupting agent (tumor-VDA), 5,6-dimethylxanthenone-4-acetic acid (DMXAA; ASA404) and correlated with tumor necrosis and treatment outcome. CE-US was performed using microbubbles (Vevo MicroMarker®) to assess the change in relative tumor blood volume following VDA treatment.
Results:
A marked decrease (up to 68% of baseline) in T1-enhancement of FaDu tumors was observed 1 day after VDA therapy indicative of a reduction in blood flow. Early (24 h) vascular response of individual tumors to VDA therapy detected by MRI correlated with tumor necrosis and volume estimates at 10 days post treatment. VDA treatment also resulted in a significant reduction in AUC and amplitude of patient tumor-derived SCCHN xenografts. Consistent with MRI observations, CE-US revealed a significant reduction in tumor blood volume of patient tumor-derived SCCHN xenografts after VDA therapy. Treatment with VDA resulted in a significant tumor growth inhibition of patient tumor derived SCCHN xenografts.
Conclusions:
These findings demonstrate that both CE-MRI and CE-US allow monitoring of early changes in vascular function following VDA therapy. The results also demonstrate, for the first time, potent vascular disruptive and antitumor activity of DMXAA against patient tumor-derived head and neck carcinoma xenografts.
Insights
Contrast-enhanced MRI and ultrasound imaging effectively monitor blood flow changes in head and neck cancer xenografts after vascular disrupting agent therapy. This approach reveals early tumor response and correlates with treatment outcomes.
Area of Science:
- Oncology
- Medical Imaging
- Pharmacology
Background:
- Squamous cell carcinoma of the head and neck (SCCHN) xenografts were studied to assess blood flow changes non-invasively.
- Contrast-enhanced magnetic resonance (MR) and ultrasound (US) imaging were employed for monitoring.
- The study focused on changes in tumor vascularity following treatment with a vascular disrupting agent.
Purpose of the Study:
- To evaluate the efficacy of contrast-enhanced MR and US imaging in monitoring tumor blood flow.
- To assess the early vascular response of SCCHN xenografts to a tumor-vascular disrupting agent (VDA).
- To correlate imaging findings with tumor necrosis and treatment outcomes.
Main Methods:
- Mice bearing FaDu tumors and patient-derived SCCHN xenografts were used.
- MR imaging utilized gadofosveset trisodium to measure changes in T1-relaxation rate (ΔR1) and enhancement parameters (amplitude, AUC).
- Contrast-enhanced ultrasound (CE-US) with microbubbles assessed changes in relative tumor blood volume post-VDA treatment.
Main Results:
- A significant decrease in tumor T1-enhancement (up to 68%) was observed 24 hours after VDA therapy, indicating reduced blood flow.
- Early vascular response detected by MRI correlated with tumor necrosis and volume at 10 days post-treatment.
- Both CE-MRI and CE-US showed a significant reduction in tumor blood volume and enhancement after VDA treatment, leading to tumor growth inhibition.
Conclusions:
- Contrast-enhanced MRI and CE-US are effective tools for monitoring early vascular function changes after VDA therapy.
- The study demonstrated the potent vascular disruptive and antitumor activity of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) against patient-derived head and neck carcinoma xenografts.
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