Reduction of vascular and permeable regions in solid tumors detected by macromolecular contrast magnetic resonance imaging after treatment with antiangiogenic agent TNP-470.
OBJECTIVE
The availability of noninvasive techniques to detect the effects of antiangiogenic agents is critically important for optimizing treatment of cancer with these agents. Magnetic resonance imaging (MRI) is one such noninvasive technique that is routinely used clinically.


METHODS
In this study, we have evaluated the use of MRI of the intravascular contrast agent albumin-GdDTPA to detect the effects of the antiangiogenic agent TNP-470 on the vascular volume and permeability of the MatLyLu prostate cancer model.


RESULTS
TNP-470-treated tumors demonstrated a significant decrease of vascular volume, as well as a significant reduction in vascular and permeable regions, compared with volume-matched control tumors. Although the fractional volume of permeable regions in the tumor decreased, the average value of tumor permeability did not decrease significantly. This was attributable to increase in permeability in some regions of the tumor. These regions were mostly associated with low vascular volume. ELISA assays of control and treated MatLyLu tumors also detected a significant increase of vascular endothelial growth factor in the TNP-470-treated tumors.


CONCLUSIONS
MRI detected significant changes in tumor vascular characteristics after treatment with TNP-470.
Bhujwalla
Zaver M
ZM
Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. zaver@mri.jhu.edu
Artemov
Dmitri
D
Natarajan
Kshama
K
Solaiyappan
Meiyappan
M
Kollars
Peggy
P
Kristjansen
Paul E G
PE
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D003287:Contrast Media / Q000494:pharmacology; D003510:Cyclohexanes; D016228:Endothelial Growth Factors / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009369:Neoplasms / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011471:Prostatic Neoplasms / Q000378:metabolism; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D000903:Antibiotics, Antineoplastic; D003287:Contrast Media; D003510:Cyclohexanes; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012717:Sesquiterpenes; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000077609:O-(Chloroacetylcarbamoyl)fumagillol