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 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Nuclear Medicine and Biology
Vol/bind	43
Udgave nummer	3
Sider (fra-til)	198-205
Antal sider	8
ISSN	0969-8051
DOI	https://doi.org/10.1016/j.nucmedbio.2015.12.002
Status	Udgivet - 1 mar. 2016

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10.1016/j.nucmedbio.2015.12.002Licens: CC BY-NC-ND

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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.

I: Nuclear Medicine and Biology, Bind 43, Nr. 3, 01.03.2016, s. 198-205.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

@article{ea9705dd996c45c3b180383abd124cc5,

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",

year = "2016",

month = mar,

day = "1",

doi = "10.1016/j.nucmedbio.2015.12.002",

language = "English",

volume = "43",

pages = "198--205",

journal = "Nuclear Medicine and Biology",

issn = "0969-8051",

publisher = "Elsevier",

number = "3",

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TY - JOUR

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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