Prediction of antiangiogenic treatment efficacy by iron oxide enhanced parametric magnetic resonance imaging.
OBJECTIVE
Tools for monitoring modern target-specific antiangiogenic and antivascular therapies are highly desirable because treatment strategies are time consuming, expensive, and yet sometimes ineffective. Therefore, the aim of this experimental study was to evaluate the predictive value of steady-state ultrasmall particles of iron oxide (USPIO; SH U 555 C)-enhanced magnetic resonance imaging (MRI) for early assessment of antivascular tumor-treatment effectiveness.


METHODS
Mice were inoculated with an HT-1080 fibrosarcoma xenograft and subjected to target-specific antivascular therapy using a selective thrombogenic vascular-targeting agent (truncated tissue factor fused to RGD peptide) or saline as control. Four to 8 hours after treatment, the USPIO-induced change in the transverse relaxation rate DeltaR2* was measured by MRI, and the vascular volume fraction (VVF) was calculated by calibrating DeltaR2* of the tumor by DeltaR2* of muscle tissue. Treatment response was defined by histologic grading of vascular thrombosis and tumor necrosis.


RESULTS
After thrombogenic treatment, half of the HT-1080 xenograft-bearing animals showed only minor (=nonresponder) whereas the other half showed extensive tumor thrombosis (=responders). For responders, a significant decrease of DeltaR2* and VVF was observed compared with the control group (DeltaR2*: controls: 16 +/- 1 s-1 vs. responder: 4 +/- 2 s-1; P < 0.001) whereas DeltaR2* and VVF remained nearly unchanged for nonresponders (DeltaR2*: nonresponder 14 +/- 2 s-1). VVF and DeltaR2* values correlated inversely with the histologic grading of vascular thrombosis and tumor necrosis (VVF: r = -0.8; DeltaR2*: r = -0.71; P < 0.01).


CONCLUSIONS
USPIO-enhanced MRI allows a noninvasive, early assessment of treatment efficacy of thrombogenic vascular-targeting agents.
Persigehl
Thorsten
T
Department of Clinical Radiology, University of Münster, Münster, Germany.
Matuszewski
Lars
L
Kessler
Torsten
T
Wall
Alexander
A
Meier
Norbert
N
Ebert
Wolfgang
W
Berdel
Wolfgang E
WE
Heindel
Walter
W
Mesters
Rolf
R
Bremer
Christoph
C
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage; D005354:Fibrosarcoma / Q000098:blood supply* / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000235:genetics; D011237:Predictive Value of Tests; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use*; D013925:Thromboplastin / Q000235:genetics; D013997:Time Factors; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D005290:Ferric Compounds; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; C526680:tTF-RGD peptide; C000499:ferric oxide; C047981:arginyl-glycyl-aspartic acid; D013925:Thromboplastin