Korean J Radiol.  2013 Aug;14(4):589-596. 10.3348/kjr.2013.14.4.589.

Dynamic Contrast-Enhanced MRI for Monitoring Antiangiogenic Treatment: Determination of Accurate and Reliable Perfusion Parameters in a Longitudinal Study of a Mouse Xenograft Model

• Song Y
• Cho G
• Suh JY
• Lee CK
• Kim YR
• Kim YJ
• Kim JK

• KMID: 1715763
• DOI: http://doi.org/10.3348/kjr.2013.14.4.589

Abstract

OBJECTIVE
To determine the reliable perfusion parameters in dynamic contrast-enhanced MRI (DCE-MRI) for the monitoring antiangiogenic treatment in mice.
MATERIALS AND METHODS
Mice, with U-118 MG tumor, were treated with either saline (n = 3) or antiangiogenic agent (sunitinib, n = 8). Before (day 0) and after (days 2, 8, 15, 25) treatment, DCE examinations using correlations of perfusion parameters (Kep, Kel, and AH from two compartment model; time to peak, initial slope and % enhancement from time-intensity curve analysis) were evaluated.
RESULTS
Tumor growth rate was found to be 129% +/- 28 in control group, -33% +/- 11 in four mice with sunitinib-treatment (tumor regression) and 47% +/- 15 in four with sunitinib-treatment (growth retardation). Kep (r = 0.80) and initial slope (r = 0.84) showed strong positive correlation to the initial tumor volume (p < 0.05). In control mice, tumor regression group and growth retardation group animals, Kep (r : 0.75, 0.78, 0.81, 0.69) and initial slope (r : 0.79, 0.65, 0.67, 0.84) showed significant correlation with tumor volume (p < 0.01). In four mice with tumor re-growth, Kep and initial slope increased 20% or greater at earlier (n = 2) than or same periods (n = 2) to when the tumor started to re-grow with 20% or greater growth rate.
CONCLUSION
Kep and initial slope may a reliable parameters for monitoring the response of antiangiogenic treatment.

Keyword

Angiogenesis; Dynamic contrast enhanced MR; Two compartment model; Tumor perfusion

MeSH Terms

Angiogenesis Inhibitors/therapeutic use
Animals
Contrast Media/*diagnostic use
Female
Heterografts
Indoles/*therapeutic use
Longitudinal Studies
Magnetic Resonance Imaging/*methods
Mice
Mice, Inbred BALB C
Neoplasm Transplantation
Neoplasms, Experimental/*diagnosis/drug therapy/pathology
Pyrroles/*therapeutic use
Reproducibility of Results
Tumor Burden
Angiogenesis Inhibitors
Contrast Media
Indoles
Pyrroles

Figure

• 

  Fig. 1 Tumor volume, Kep and initial slope according to time sequence in mouse with tumor regression by sunitinib treatment. In this mouse, tumor was not noted in days 15 and 25. A. Tumor volume versus Kep. Kep and tumor volume show similar decrease pattern after sunitinib administration. B. Mean Kep was 0.57/sec in day 0 (left), 0.74/sec in day 2 (center), and 0.24/sec in day 8 (right). C. Tumor volume versus initial slope. Initial slope and tumor volume show similar decrease pattern after sunitinib administration. D. Mean initial slope was 5575/sec in day 0 (left), 5072/sec in day 2 (center), and 1872/sec in day 8 (right).

• 

  Fig. 2 Tumor volume, Kep and initial slope according to time sequence in mouse with growth retardation by sunitinib treatment. A. Tumor volume versus Kep. Kep shows earlier rebound than tumor re-growth. B. Tumor volume versus initial slope. Initial slope shows rebound at same time of tumor re-growth.

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