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


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).


CONCLUSIONS
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.
Aliu
S O
SO
Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, California 94107, USA. sheye.aliu@radiology.ucsf.edu
Wilmes
L J
LJ
Moasser
M M
MM
Hann
B C
BC
Li
K-L
KL
Wang
D
D
Hylton
N M
NM
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D017063:Outcome Assessment, Health Care / Q000379:methods; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib