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Nucl Med Biol. 2016 Mar;43(3):198-205. doi: 10.1016/j.nucmedbio.2015.12.002. Epub 2015 Dec 22.

Comparison of (18)F-FET and (18)F-FLT small animal PET for the assessment of anti-VEGF treatment response in an orthotopic model of glioblastoma.

Author information

1
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark. Electronic address: Mette.kjoelhede.nedergaard@regionh.dk.
2
Department of Radiation Biology, The Finsen Center, Rigshospitalet, Copenhagen, Denmark.
3
Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.
4
Phase 1 Unit, Department of Oncology, The Finsen Center, Rigshospitalet, Copenhagen, Denmark.
5
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.

Abstract

BACKGROUND:

The radiolabeled amino acid O-(2-(18)F-fluoroethyl)-L-tyrosine (FET) and thymidine analogue 3'-deoxy-3'-(18)F-fluorothymidine (FLT) are widely used for positron emission tomography (PET) brain tumor imaging; however, comparative studies are scarce. The aim of this study therefore was to compare FLT and FET PET for the assessment of anti-VEGF response in glioblastoma xenografts.

METHODS:

Xenografts with confirmed intracranial glioblastoma were treated with anti-VEGF therapy (B20-4.1) or saline as control. Weekly bioluminescence imaging (BLI), FLT and FET PET/CT were used to follow treatment response. Tracer uptake of FLT and FET was quantified using maximum standardized uptake (SUVmax) values and tumor-to-background ratios (TBRs). Survival, the Ki67 proliferation index and micro-vessel density (MVD) were evaluated.

RESULTS:

In contrast to FLT TBRs, FET TBRs were significantly lower as early as one week after treatment initiation in the anti-VEGF group as compared to the control group. Following two weeks of treatment, both FLT and FET TBRs were significantly lower in the anti-VEGF group. In contrast, no significant difference between the treatment groups was detected using BLI. Furthermore, we found a significantly lower MVD in the anti-VEGF group as compared to the control group. However, we found no difference in the Ki67 proliferation index or mean survival time.

CONCLUSION:

FET appears to be a more sensitive tracer than FLT to measure early response to anti-VEGF therapy with PET. Advances in knowledge and implications for patient care FET PET appears to be an early predictor of anti-VEGF efficacy. Confirmation of these results in clinical studies is needed.

KEYWORDS:

FET; FLT; Glioblastoma; Glioma; PET; Response

PMID:
26924500
DOI:
10.1016/j.nucmedbio.2015.12.002
[Indexed for MEDLINE]
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