Yonsei Med J.  2012 Nov;53(6):1147-1153. 10.3349/ymj.2012.53.6.1147.

Quantitative Assessment of Tumor Responses after Radiation Therapy in a DLD-1 Colon Cancer Mouse Model Using Serial Dynamic Contrast-Enhanced Magnetic Resonance Imaging

• Ahn SJ
• Koom WS
• An CS
• Lim JS
• Lee SK
• Suh JS
• Song HT

• KMID: 1414257
• DOI: http://doi.org/10.3349/ymj.2012.53.6.1147

Abstract

PURPOSE
The purpose of this study was to investigate the predictability of pretreatment values including Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) derived parameters (Ktrans, Kep and Ve), early changes in parameters (Ktrans, tumor volume), and heterogeneity (standard deviation of Ktrans) for radiation therapy responses via a human colorectal cancer xenograft model.
MATERIALS AND METHODS
A human colorectal cancer xenograft model with DLD-1 cancer cells was produced in the right hind limbs of five mice. Tumors were irradiated with 3 fractions of 3 Gy each for 3 weeks. Baseline and follow up DCE-MRI were performed. Quantitative parameters (Ktrans, Kep and Ve) were calculated based on the Tofts model. Early changes in Ktrans, standard deviation (SD) of Ktrans, and tumor volume were also calculated. Tumor responses were evaluated based on histology. With a cut-off value of 0.4 for necrotic factor, a comparison between good and poor responses was conducted.
RESULTS
The good response group (mice #1 and 2) exhibited higher pretreatment Ktrans than the poor response group (mice #3, 4, and 5). The good response group tended to show lower pretreatment Kep, higher pretreatment Ve, and larger baseline tumor volume than the poor response group. All the mice in the good response group demonstrated marked reductions in Ktrans and SD value after the first radiation. All tumors showed increased volume after the first radiation therapy.
CONCLUSION
The good response after radiation therapy group in the DLD-1 colon cancer xenograft nude mouse model exhibited a higher pretreatment Ktrans and showed an early reduction in Ktrans, demonstrating a more homogenous distribution.

Keyword

Colorectal cancer; radiation therapy; magnetic resonance imaging; permeability; angiogenesis

MeSH Terms

Animals
Colonic Neoplasms/*pathology/*radiotherapy
Female
Humans
Magnetic Resonance Imaging/*methods
Mice
Mice, Nude
Xenograft Model Antitumor Assays

Figure

• 

  Fig. 1 An exceptional case, mouse #3, was assigned to the poor response group although it showed a large area of necrosis (NF=0.49). (A) Serial DCE-MRI with color mapping shows the change in Ktrans. Pretreatment Ktrans showed a relatively low value (0.11). Ktrans increased after the first radiation therapy (K1R=1.51). Red color represents the higher value of Ktrans and blue color represents the lower value. An outgrowing tumor was identified after the first radiation therapy (arrow). (B) H&E staining of the newly grown tumor, which separated from the main mass, showed rare necrosis. The original magnification is ×2. The red line indicates the tumor border and the blue line indicates the area of necrosis. NF, necrotic fraction; H&E, hematoxylin and eosin.

• 

  Fig. 2 Comparison of quantitative parameters between the good and the poor response groups upon baseline imaging. (A) Ktrans, (B) Kep, (C) Ve, (D) pretreatment tumor volume.

• 

  Fig. 3 Comparison of Ktrans between the good and the poor response groups after the 1st radiation therapy. (A) Early changes in Ktrans and (B) early changes in standard deviation for Ktrans (SD). The y-axis represents the ratio of the value after the 1st radiation therapy to the pretreatment value. The horizontal solid line at the ratio of 1 represents no change within the interval.

• 

  Fig. 4 A representative case of good response in mouse #2. (A) Serial DCE-MRI with color mapping shows higher pretreatment Ktrans (0.29) and marked reduction in Ktrans after the first radiation therapy (K1R=0.47). (B) H&E staining of the corresponding section in mouse #2. The original magnification is ×2. Necrosis is identified in the center of the tumor. The red line indicates the tumor border and the blue line indicates the area of necrosis. The necrosis factor was 0.46. Histogram shows the heterogeneous distribution of Ktrans at baseline with an SD of 0.09 (C) and the homogenous distribution of Ktrans with an SD of 0.05 after the first radiation therapy (D). DCE-MRI, dynamic contrast-enhanced magnetic resonance imaging; SD, standard deviation; H&E, hematoxylin and eosin.

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