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.
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.
['Nedergaard|Mette Kjoelhede|MK|', 'Michaelsen|Signe Regner|SR|', 'Perryman|Lara|L|', 'Erler|Janine|J|', 'Poulsen|Hans Skovgaard|HS|', 'Stockhausen|Marie-Thérése|MT|', 'Lassen|Ulrik|U|', 'Kjaer|Andreas|A|']
D000818:Animals D000068258:Bevacizumab D001932:Brain Neoplasms D002471:Cell Transformation, Neoplastic D015224:Dideoxynucleosides D005260:Female D005909:Glioblastoma D057809:HEK293 Cells D006801:Humans D051379:Mice D055806:Microvessels D049268:Positron-Emission Tomography D016019:Survival Analysis D014443:Tyrosine D042461:Vascular Endothelial Growth Factor A
PET Response Glioblastoma FET FLT Glioma