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Updated: Jul 6, 2026
Intravital Microscopy of Tumor-associated Vasculature Using Advanced Dorsal Skinfold Window Chambers on Transgenic Fluorescent Mice
Published on: January 19, 2018
Contrast enhanced MRI and intravital fluorescence microscopy indicate improved tumor microcirculation in highly
M E Eichhorn1, S Strieth, S Luedemann
1Department of Surgery, Klinikum Grosshadern, University of Munich (LMU), Germany. martin.eichhorn@med.uni-muenchen.de
Abstract:
Anti-angiogenic therapy by blocking VEGF signalling combined with standard chemotherapy is a novel strategy for clinical cancer treatment. The mechanisms for enhanced antitumoral effects are still a matter of controversial debate. Tumor vessel "normalization" upon anti-angiogenic therapy leading to improved drug delivery has been proposed as possible mechanism. Therefore, aim of the study was to investigate tumor microvascular function upon anti-VEGFR treatment in highly vascularized melanomas. A detailed intravital-microscopic analysis of tumor microcirculation including the distribution pattern of vessel diameters and blood flow velocities was performed in melanomas grown in dorsal skinfold chambers of hamsters. Animals with highly vascularized established tumors were treated by a VEGFR tyrosin kinase inhibitor (SU5416) on 3 repetitive days. Tumor tissue oxygenation was measured by phosphorescence quenching technique. Overall tumor microcirculation of subcutaneous tumors was investigated by contrast enhanced MRI (CE-MRI). Vessel density was significantly decreased in treated animals. A significant shift in the distribution patterns towards increased vessel diameters and faster red blood cell velocities in remaining tumor vessels was observed upon anti-VEGF treatment, compensating reduced vascular density. Moreover, a trend towards elevated pO(2) levels in treated tumors was observed. Compared to controls, inflow kinetics of tumors quantified by CE-MRI as well as overall uptake of contrast agent in tumor tissue were significantly increased following short-term SU5416 treatment. In conclusion the results confirm temporarily improved tumor microvascular function in highly vascularized melanomas upon short term anti-VEGFR treatment leading to enhanced tumor blood supply and oxygenation potentially improving the efficacy of simultaneous chemo- or radiotherapy.
Insights
Anti-VEGF therapy, combined with chemotherapy, may improve cancer treatment by normalizing tumor blood vessels. This study shows short-term treatment enhances blood flow and oxygenation in melanomas, potentially boosting drug delivery and treatment efficacy.
Area of Science:
- Oncology
- Vascular Biology
- Cancer Therapeutics
Background:
- Anti-angiogenic therapy targeting Vascular Endothelial Growth Factor Receptor (VEGFR) signaling is a novel cancer treatment strategy.
- The precise mechanisms by which anti-VEGF therapy enhances anti-tumoral effects, such as tumor vessel normalization and improved drug delivery, remain debated.
Purpose of the Study:
- To investigate the impact of anti-VEGFR treatment on tumor microvascular function in highly vascularized melanomas.
- To assess changes in tumor microcirculation, blood flow, and oxygenation following VEGFR tyrosine kinase inhibitor treatment.
Main Methods:
- Intravital microscopy was used to analyze tumor microcirculation, including vessel diameter and blood flow velocity, in hamster melanomas.
- Tumor tissue oxygenation was measured using phosphorescence quenching.
- Contrast-enhanced MRI (CE-MRI) evaluated overall tumor microcirculation and contrast agent uptake.
Main Results:
- Anti-VEGFR treatment (SU5416) led to decreased vessel density but increased vessel diameters and red blood cell velocities in remaining tumor vessels.
- A trend towards elevated tumor tissue oxygenation (pO2) was observed.
- CE-MRI revealed significantly increased tumor inflow kinetics and contrast agent uptake post-treatment.
Conclusions:
- Short-term anti-VEGFR treatment temporarily improves microvascular function in highly vascularized melanomas.
- Enhanced tumor blood supply and oxygenation suggest improved efficacy for concurrent chemotherapy or radiotherapy.
