Laboraroty Animal Research

Korean Association for Laboratory Animal Science (한국실험동물학회)
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[18F]FET PET is a useful tool for treatment evaluation and prognosis prediction of anti-angiogenic drug in an orthotopic glioblastoma mouse model

  • Kim, Ok-Sun (Korea Drug Development Platform using Radio-isotope, Korea Institute of Radiological & Medical Sciences) ;
  • Park, Jang Woo (Korea Drug Development Platform using Radio-isotope, Korea Institute of Radiological & Medical Sciences) ;
  • Lee, Eun Sang (Korea Drug Development Platform using Radio-isotope, Korea Institute of Radiological & Medical Sciences) ;
  • Yoo, Ran Ji (Korea Drug Development Platform using Radio-isotope, Korea Institute of Radiological & Medical Sciences) ;
  • Kim, Won-Il (College of Veterinary Medicine, Chonbuk National University) ;
  • Lee, Kyo Chul (Division of Applied RI, Korea Institute of Radiological & Medical Sciences) ;
  • Shim, Jae Hoon (Korea Drug Development Platform using Radio-isotope, Korea Institute of Radiological & Medical Sciences) ;
  • Chung, Hye Kyung (Korea Drug Development Platform using Radio-isotope, Korea Institute of Radiological & Medical Sciences)
  • Received : 2018.10.22
  • Accepted : 2018.12.07
  • Published : 2018.12.31
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Abstract

O-2-$^{18}F$-fluoroethyl-l-tyrosine ($[^{18}F]FET$) 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 $[^{18}F]FET$ 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 $[^{18}F]FET$ 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 $[^{18}F]FET$ PET is a sensitive method to monitor the response of GBM bearing mice to anti-angiogenic drug. Moreover, $[^{18}F]FET$ 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 $[^{18}F]FET$ 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.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

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