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MRI methods for evaluating the effects of tyrosine kinase inhibitor administration used to enhance chemotherapy efficiency in a breast tumor xenograft model

✍ Scribed by S.O. Aliu; L.J. Wilmes; M.M. Moasser; B.C. Hann; K.-L. Li; D. Wang; N.M. Hylton


Publisher
John Wiley and Sons
Year
2009
Tongue
English
Weight
472 KB
Volume
29
Category
Article
ISSN
1053-1807

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✦ Synopsis


Abstract

Purpose

To evaluate whether quantitative MRI parameters are sensitive to the effects of the tyrosine kinase inhibitor gefitinib and can discriminate between two different treatment protocols.

Materials and Methods

Untreated mice with BT474 breast tumor xenografts were characterized in a preliminary study. Subsequently, tumor volume, apparent diffusion coefficient (ADC), transendothelial permeability (K^ps^), and fractional plasma volume (fPV) were measured in three groups of mice receiving: 1) control vehicle for 10 days, or gefitinib as 2) a single daily dose for 10 days or 3) a 2‐day pulsed dose.

Results

Gefitinib treatment resulted in significant tumor growth inhibition (pulsed: 439 ± 93; daily: 404 ± 53; control: 891 ± 174 mm^3^, P < 0.050) and lower cell density (pulsed: 0.15 ± 0.01, daily: 0.17 ± 0.01, control: 0.24 ± 0.01, P < 0.050) after 9 days. Tumor ADC increased in treated groups but decreased in controls (P > 0.050). Tumor K^ps^ decreased with pulsed treatment but rebounded afterwards and increased with daily treatment (P > 0.050). Tumor fPV increased in both treated groups, decreasing afterwards with pulsed treatment (P > 0.050).

Conclusion

Quantitative MRI can provide a sensitive measure of gefitinib‐induced tumor changes, potentially distinguish between treatment regimens, and may be useful for determining optimal treatment scheduling for enhancing chemotherapy delivery. J. Magn. Reson. Imaging 2009;29:1071–1079. © 2009 Wiley‐Liss, Inc.