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

Abstract

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

Surgical resection of glioblastomas induces pleiotrophin-mediated self-renewal of glioblastoma stem cells in recurrent tumors

“…18 F-FET PET has been used for tumor imaging in several preclinical GBM models with both murine- and human-derived cell cultures, and its sensitivity was found slightly superior to bioluminescent imaging approaches. 26 , 27 This tracer therefore shows promise as an alternative imaging modality in preclinical brain tumor studies, as 18 F-FET PET does not require preceding luciferase transfection of tumor cells necessary for bioluminescent imaging approaches.…”

Use of multimodality imaging, histology, and treatment feasibility to characterize a transgenic Rag2-null rat model of glioblastoma

“…In addition, Kim et al. demonstrated the superiority of 18 F-FET PET for therapy assessment and prognostication compared with bioluminescence (BLI) or MRI when evaluating an antiangiogenic drug, bevacizumab, in an intracranial U87 GBM Nude mouse model ( 37 ). In mice with intracranial U251 GBM implants, PET and MRI were used to test the potential of poly(ADP-ribose) polymerase (PARP)-targeted PET radiotracer 18 F-PARPi, which discriminated radiation injury from tumor better than 18 F-FET in the contrast-enhanced portion of the brain ( 38 ).…”