Artikel
Anti-angiogenic therapy using SU11248 improves microvascular delivery of chemotherapy in surviving glioma vasculature
Antiangiogene Therapie mittels SU 11248 verbessert die mikrovaskuläre Anflutung von Chemotherapie in den überlebenden Gliomgefäßen
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Veröffentlicht: | 30. Mai 2008 |
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Objective: SU11248 represents a promising anti-angiogenic therapy option for the treatment of malignant glioma. The aim of the study was to characterize the effects of Sutent on glioma microcirculation and microvascular delivery of chemotherapy.
Methods: For intravital microscopic analysis glioma cells were implanted into dorsal skinfold chambers (n=8 per group). Treatment was initiated 7 days after implantation. Analysis included total (TVD) and functional (FVD) vessel densities, perfusion index (PI), microvascular diameter (D) and blood flow rate (Q). Delivery of doxorubicin was investigated by analysing microvascular delivery of doxorubicin to interstitium (MD) and microvascular delivery index (MDI) of surviving tumor vasculature. Effects on tumor growth were characterized by sc implantation.
Results: SU11248 significantly reduced tumor growth due to anti-angiogenic and anti-vascular properties (TVD 110±62cm/cm2 vs. 298±12cm/cm2; FVD 211±46cm/cm2 vs 90±45cm/cm2). Therapy surviving vessels displayed significantly improved microhemodynamic characteristics (PI: 63%±7 vs. 78%±10, D: 10±3µm vs. 16±6µm; Q: 35±26nl/sec vs. 368±253nl/sec). These alterations resulted in a significantly increased MDI (0.59±0.19 vs. 0.20±0.07) of surviving vasculature. Therefore, MD was maintained despite reduced FVD.
Conclusions: SU11248 treatment improves the delivery process of chemotherapy in surviving tumor vessels by altering microvascular hemodynamics and significantly inhibits glioma growth by anti-angiogenic and anti-vascular properties. These effects might be exploited for future combined therapy procedures in clinical glioma treatment.