Paclitaxel encapsulated in cationic lipid complexes (MBT-0206) impairs functional tumor vascular properties as detected by dynamic contrast enhanced magnetic resonance imaging.
Cationic lipid complexes have been shown to be bound and internalized selectively by angiogenic tumor endothelial cells after intravenous injection. Based on this phenomenon, the chemotherapeutic agent paclitaxel was encapsulated into these lipid complexes providing a vascular targeting agent (MBT-0206). As noninvasive imaging techniques are of critical importance for optimizing antivascular cancer treatment in the clinic, we have evaluated the antivascular effects of MBT-0206 in the A-MEL-3 solid tumor model using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Twenty-four hours after three intravenous applications of MBT-0206, tumors of treated animals demonstrated a significant decrease of intratumoral blood volume and an increase of vascular permeability in comparison to size-matched control tumors. In contrast, animals treated with conventional paclitaxel given as Taxol at equal drug dose did not show any significant differences in vascular parameters acquired by DCE-MRI in comparison to controls. Immunohistological analysis confirmed a significant reduction of microvessel density in MBT-0206 treated tumors. Moreover, a significant increase of intratumoral microvascular occlusion following MBT-0206 treatment was observed compared to controls and paclitaxel treated animals. In conclusion, antivascular tumor therapy with MBT-0206 significantly impairs functional tumor microcirculation. DCE-MRI is a promising tool to quantify the antivascular effects of MBT-0206 during treatment.
Eichhorn
M E
ME
Department of Surgery, Institute for Surgical Research, Klinikum Grosshadern, University of Munich, Munich, Germany.
Becker
S
S
Strieth
S
S
Werner
A
A
Sauer
B
B
Teifel
M
M
Ruhstorfer
H
H
Michaelis
U
U
Griebel
J
J
Brix
G
G
Jauch
K-W
KW
Dellian
M
M
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002214:Capsules / Q000008:administration & dosage; D003287:Contrast Media / Q000493:pharmacokinetics*; D006224:Cricetinae; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D008055:Lipids / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008545:Melanoma / Q000098:blood supply* / Q000188:drug therapy; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage*; D012878:Skin Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D002214:Capsules; D003287:Contrast Media; D008055:Lipids; C511389:MBT-0206; D019786:Gadolinium DTPA; D017239:Paclitaxel