We have previously shown that the dense vascular network in mouse brain allows for growth of human
melanoma xenografts (Mel57) by co-option of preexisting vessels. Overexpression of recombinant
vascular endothelial growth factor-A (
VEGF-A) by such xenografts induced functional and morphologic alterations of preexisting vessels. We now describe the effects of
VEGF-A expression on visualization of these
brain tumors in mice by magnetic resonance imaging (MRI), using
gadolinium diethylenetriaminepenta-acetic acid (
Gd-DTPA) and ultra small paramagnetic
iron oxide particles (
USPIO) as
contrast agents. Brain lesions derived from (mock-transfected) Mel57 cells were undetectable in MRI after
Gd-DTPA injection. However, the majority of such lesions became visible after injection of
USPIO, due to the lower vascular density in the lesions as compared to the surrounding parenchyma. In contrast,
VEGF-A-expressing lesions were visualized using
Gd-DTPA-enhanced MRI by a rapid circumferential enhancement, due to leaky peritumoral vasculature.
USPIO-enhanced MRI of these
tumors corroborated the immunohistochemic finding that peritumorally located, highly irregular and dilated vessels were present, while intratumoral vessel density was low. Our study shows that
VEGF-A is a key factor in imaging of
brain neoplasms. Our data also demonstrate that, at least in brain, blood-pool agent-enhanced MRI may be a valuable diagnostic tool to detect
malignancies that are not visible on
Gd-DTPA-enhanced MRI. Furthermore, the involvement of
VEGF-A in MRI visibility suggests that care must be taken with MRI-based evaluation of antiangiogenic
therapy, as anti-
VEGF treatment might revert a
tumor to a co-opting phenotype, resulting in loss of contrast enhancement in MRI.