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

Mette Kjoelhede Nedergaard; Signe Regner Michaelsen; Lara Perryman; Janine Erler; Hans Skovgaard Poulsen; Marie-Thérése Stockhausen; Ulrik Lassen; Andreas Kjaer

doi:10.1016/j.nucmedbio.2015.12.002

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

Mette Kjoelhede Nedergaard, Signe Regner Michaelsen, Lara Perryman, Janine Erler, Hans Skovgaard Poulsen, Marie-Thérése Stockhausen, Ulrik Lassen, Andreas Kjaer

7 Citations (Scopus)

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.

Original language	English
Journal	Nuclear Medicine and Biology
Volume	43
Issue number	3
Pages (from-to)	198-205
Number of pages	8
ISSN	0969-8051
DOIs	https://doi.org/10.1016/j.nucmedbio.2015.12.002
Publication status	Published - 1 Mar 2016

Keywords

Journal Article
Research Support, Non-U.S. Gov't

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Nedergaard, M. K., Michaelsen, S. R., Perryman, L., Erler, J., Poulsen, H. S., Stockhausen, M.-T., Lassen, U., & Kjaer, A. (2016). 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. Nuclear Medicine and Biology, 43(3), 198-205. https://doi.org/10.1016/j.nucmedbio.2015.12.002

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. / Nedergaard, Mette Kjoelhede; Michaelsen, Signe Regner; Perryman, Lara et al.
In: Nuclear Medicine and Biology, Vol. 43, No. 3, 01.03.2016, p. 198-205.

Research output: Contribution to journal › Journal article › Research › peer-review

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title = "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",

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 = "Journal Article, Research Support, Non-U.S. Gov't",

author = "Nedergaard, {Mette Kjoelhede} and Michaelsen, {Signe Regner} and Lara Perryman and Janine Erler and Poulsen, {Hans Skovgaard} and Marie-Th{\'e}r{\'e}se Stockhausen and Ulrik Lassen and Andreas Kjaer",

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T1 - 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

AU - Nedergaard, Mette Kjoelhede

AU - Michaelsen, Signe Regner

AU - Perryman, Lara

AU - Erler, Janine

AU - Poulsen, Hans Skovgaard

AU - Stockhausen, Marie-Thérése

AU - Lassen, Ulrik

AU - Kjaer, Andreas

PY - 2016/3/1

Y1 - 2016/3/1

N2 - 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.

AB - 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.

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.nucmedbio.2015.12.002

DO - 10.1016/j.nucmedbio.2015.12.002

M3 - Journal article

C2 - 26924500

SN - 0969-8051

VL - 43

SP - 198

EP - 205

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

IS - 3

ER -

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

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