Lab Anim Res.  2018 Dec;34(4):248-256. 10.5625/lar.2018.34.4.248.

[¹⁸F]FET PET is a useful tool for treatment evaluation and prognosis prediction of anti-angiogenic drug in an orthotopic glioblastoma mouse model

• Kim OS
• Park JW
• Lee ES
• Yoo RJ
• Kim WI
• Lee KC
• Shim JH
• Chung HK

• KMID: 2459302
• DOI: http://doi.org/10.5625/lar.2018.34.4.248

Abstract

O-2-¹â¸F-fluoroethyl-l-tyrosine ([¹â¸F]FET) has been widely used for glioblastomas (GBM) in clinical practice, although evaluation of its applicability in non-clinical research is still lacking. The objective of this study was to examine the value of [¹â¸F]FET for treatment evaluation and prognosis prediction of anti-angiogenic drug in an orthotopic mouse model of GBM. Human U87MG cells were implanted into nude mice and then bevacizumab, a representative anti-angiogenic drug, was administered. We monitored the effect of anti-angiogenic agents using multiple imaging modalities, including bioluminescence imaging (BLI), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET/CT). Among these imaging methods analyzed, only [¹â¸F]FET uptake showed a statistically significant decrease in the treatment group compared to the control group (P=0.02 and P=0.03 at 5 and 20 mg/kg, respectively). This indicates that [¹â¸F]FET PET is a sensitive method to monitor the response of GBM bearing mice to anti-angiogenic drug. Moreover, [¹â¸F]FET uptake was confirmed to be a significant parameter for predicting the prognosis of anti-angiogenic drug (P=0.041 and P=0.007, on Days 7 and 12, respectively, on Pearson's correlation; P=0.048 and P=0.030, on Days 7 and 12, respectively, on Cox regression analysis). However, results of BLI or MRI were not significantly associated with survival time. In conclusion, this study suggests that [¹â¸F]FET PET imaging is a pertinent imaging modality for sensitive monitoring and accurate prediction of treatment response to anti-angiogenic agents in an orthotopic model of GBM.

Keyword

[¹⁸F]FET PET; glioblastoma; bevacizumab; anti-angiogenic drug; orthotopic model

MeSH Terms

Animals
Bevacizumab
Electrons
Glioblastoma*
Humans
Magnetic Resonance Imaging
Methods
Mice*
Mice, Nude
Prognosis*
Bevacizumab

Figure

• 

  Figure 1 Timeline of the experimental design. The initiation date of treatment was considered as Day 0. Grey boxes indicate bevacizumab administration (one time per day). Arrows indicate imaging modalities taken.

• 

  Figure 2 Monitoring response to anti-angiogenic drug in GBM bearing mice by BLI. Representative BLI images showing bevacizumab response on Days 0, 7, and 12 after initiation of treatment (A). Mice received 0, 5 or 20 mg/kg bevacizumab from 17 days after U87MG cell inoculation. Scale bar represents 107–108 photons/sec/cm2/sr. Bioluminescence signal in tumor of each group over time is shown (B). Values represent mean±SD of each group.

• 

  Figure 3 Monitoring the response to anti-angiogenic drug in GBM bearing mice by MRI. Representative transverse plane of T2 weighted MRI images showing bevacizumab response on Days 0, 7, and 12 after initiation of treatment (A). Tumor volume (B) and tumor growth rate (C) of each group over time are shown. Values represent mean±SD of each group.

• 

  Figure 4 Monitoring the response to anti-angiogenic drug in GBM bearing mice by [18F]FET PET imaging. Representative transverse plane of PET image showing bevacizumab response on Days 7 and 12 after initiation of treatment (A). Scale bar represents 0.5–2.0 g/mL of [18F]FET. Quantitative [18F]FET uptake in tumor of each group over time is shown (B). Values represent mean±SD of each group. *P<0.05 vs. control group determined by the Dunnett's test after ANOVA multiple comparison.

• 

  Figure 5 Kaplan-Meier survival curves for control or bevacizumab treatment groups of GBM orthotopic model. *P<0.05 vs. control group determined by log-rank test.

• 

  Figure 6 Dispersion charts demonstrating correlation between survival time and maximum SUV of [18F]FET on Days 7 (A) and 12 (B) in the orthotopic GBM model (n=8 and 11, respectively).

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