<p>Our previous studies revealed molecular alterations of
tumor vessels, varying from immature to mature alterations, resulting from
Abraxane, and demonstrated that the integrin-specific PET tracer <sup>18</sup>F-FPPRGD2
can be used to noninvasively monitor such changes. However, changes in the tumor
vasculature at functional levels such as perfusion and permeability are also important
for monitoring Abraxane treatment outcomes in patients with cancer. The purpose
of this study is to further investigate the vascular response during Abraxane
therapy and the effectiveness of its synergistic interaction with cisplatin using
Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI). Thirty MDA-MB-435
tumor mice were randomized into three groups: PBS control (C group), Abraxane
only (A group), and sequential treatment with Abraxane followed by cisplatin
(A-P group). Tumor volume was monitored based on caliper measurements. A DCE-MRI
protocol was performed at baseline and day 3. The K<sup>trans</sup>, K<sub>ep</sub>
and V<sub>e</sub> were calculated and compared with CD31, α-SMA, and Ki67
histology data. Sequential treatment with Abraxane followed by cisplatin produced
a significantly greater inhibition of tumor growth during the three weeks of
the observation period. Decreases in K<sup>trans</sup> and K<sub>ep </sub>for
the A and A-P groups were observed on day 3. Immunohistological staining suggested
vascular remodeling during the Abraxane therapy. The changes in K<sup>trans</sup>
and K<sub>ep</sub> values were correlated with alterations in the permeability
of the tumor vasculature induced by the Abraxane treatment. In conclusion,
Abraxane-mediated permeability variations in tumor vasculature can be
quantitatively visualized by DCE-MRI, making this a
useful method for studying the effects of early cancer treatment, especially
the early vascular response. Vascular remodeling by Abraxane improves
the efficiency of cisplatin delivery and thus results in a favorable
treatment outcome. </p
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