Multiregional tumor drug-uptake imaging by PET and microvascular morphology in end-stage diffuse intrinsic pontine glioma

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Inadequate tumor uptake of the vascular endothelial growth factor (VEGF) antibody bevacizumab could explain lack of effect in diffuse intrinsic pontine glioma (DIPG). Methods: By combining data from a positron emission tomography (PET) imaging study using zirconium-89(89Zr)-labeled bevacizumab and an autopsy study, a 1-on-1 analysis of multiregional in vivo and ex vivo 89Zr-bevacizumab uptake, tumor histology and vascular morphology in a DIPG patient was performed. Results: In vivo 89Zr-bevacizumab measurements showed heterogeneity between lesions. Additional ex vivo measurements and immunohistochemistry of cervicomedullary metastasis samples, showed highest uptake in the area with marked microvascular proliferation. In the primary pontine tumor all samples showed similar vascular morphology. Other histological features were similar between samples studied. Conclusion: In vivo bevacizumab-PET serves to identify heterogeneous uptake between tumor lesions, while subcentimeter intra-lesional heterogeneity could only be identified by ex vivo measurements. Bevacizumab uptake is enhanced by vascular proliferation, although our results suggest it is not the only determinant of intra-lesional uptake heterogeneity.

Original languageEnglish
Pages (from-to)612-615
JournalJournal of Nuclear Medicine
Volume59
Issue number4
Early online date17 Aug 2017
DOIs
Publication statusPublished - Apr 2018

Cite this

@article{c294c81adbf4473bbc98a69909f31ad3,
title = "Multiregional tumor drug-uptake imaging by PET and microvascular morphology in end-stage diffuse intrinsic pontine glioma",
abstract = "Inadequate tumor uptake of the vascular endothelial growth factor (VEGF) antibody bevacizumab could explain lack of effect in diffuse intrinsic pontine glioma (DIPG). Methods: By combining data from a positron emission tomography (PET) imaging study using zirconium-89(89Zr)-labeled bevacizumab and an autopsy study, a 1-on-1 analysis of multiregional in vivo and ex vivo 89Zr-bevacizumab uptake, tumor histology and vascular morphology in a DIPG patient was performed. Results: In vivo 89Zr-bevacizumab measurements showed heterogeneity between lesions. Additional ex vivo measurements and immunohistochemistry of cervicomedullary metastasis samples, showed highest uptake in the area with marked microvascular proliferation. In the primary pontine tumor all samples showed similar vascular morphology. Other histological features were similar between samples studied. Conclusion: In vivo bevacizumab-PET serves to identify heterogeneous uptake between tumor lesions, while subcentimeter intra-lesional heterogeneity could only be identified by ex vivo measurements. Bevacizumab uptake is enhanced by vascular proliferation, although our results suggest it is not the only determinant of intra-lesional uptake heterogeneity.",
keywords = "Journal Article",
author = "{Veldhuijzen van Zanten}, {Sophie E M} and Sewing, {A Charlotte P} and {van Lingen}, Arthur and Hoekstra, {Otto S} and Pieter Wesseling and Meel, {Micha{\"e}l H} and {van Vuurden}, {Dannis G} and Kaspers, {Gertjan J L} and Esther Hulleman and Marianna Bugiani",
note = "Copyright {\circledC} 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.",
year = "2018",
month = "4",
doi = "10.2967/jnumed.117.197897",
language = "English",
volume = "59",
pages = "612--615",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "4",

}

TY - JOUR

T1 - Multiregional tumor drug-uptake imaging by PET and microvascular morphology in end-stage diffuse intrinsic pontine glioma

AU - Veldhuijzen van Zanten, Sophie E M

AU - Sewing, A Charlotte P

AU - van Lingen, Arthur

AU - Hoekstra, Otto S

AU - Wesseling, Pieter

AU - Meel, Michaël H

AU - van Vuurden, Dannis G

AU - Kaspers, Gertjan J L

AU - Hulleman, Esther

AU - Bugiani, Marianna

N1 - Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

PY - 2018/4

Y1 - 2018/4

N2 - Inadequate tumor uptake of the vascular endothelial growth factor (VEGF) antibody bevacizumab could explain lack of effect in diffuse intrinsic pontine glioma (DIPG). Methods: By combining data from a positron emission tomography (PET) imaging study using zirconium-89(89Zr)-labeled bevacizumab and an autopsy study, a 1-on-1 analysis of multiregional in vivo and ex vivo 89Zr-bevacizumab uptake, tumor histology and vascular morphology in a DIPG patient was performed. Results: In vivo 89Zr-bevacizumab measurements showed heterogeneity between lesions. Additional ex vivo measurements and immunohistochemistry of cervicomedullary metastasis samples, showed highest uptake in the area with marked microvascular proliferation. In the primary pontine tumor all samples showed similar vascular morphology. Other histological features were similar between samples studied. Conclusion: In vivo bevacizumab-PET serves to identify heterogeneous uptake between tumor lesions, while subcentimeter intra-lesional heterogeneity could only be identified by ex vivo measurements. Bevacizumab uptake is enhanced by vascular proliferation, although our results suggest it is not the only determinant of intra-lesional uptake heterogeneity.

AB - Inadequate tumor uptake of the vascular endothelial growth factor (VEGF) antibody bevacizumab could explain lack of effect in diffuse intrinsic pontine glioma (DIPG). Methods: By combining data from a positron emission tomography (PET) imaging study using zirconium-89(89Zr)-labeled bevacizumab and an autopsy study, a 1-on-1 analysis of multiregional in vivo and ex vivo 89Zr-bevacizumab uptake, tumor histology and vascular morphology in a DIPG patient was performed. Results: In vivo 89Zr-bevacizumab measurements showed heterogeneity between lesions. Additional ex vivo measurements and immunohistochemistry of cervicomedullary metastasis samples, showed highest uptake in the area with marked microvascular proliferation. In the primary pontine tumor all samples showed similar vascular morphology. Other histological features were similar between samples studied. Conclusion: In vivo bevacizumab-PET serves to identify heterogeneous uptake between tumor lesions, while subcentimeter intra-lesional heterogeneity could only be identified by ex vivo measurements. Bevacizumab uptake is enhanced by vascular proliferation, although our results suggest it is not the only determinant of intra-lesional uptake heterogeneity.

KW - Journal Article

U2 - 10.2967/jnumed.117.197897

DO - 10.2967/jnumed.117.197897

M3 - Article

VL - 59

SP - 612

EP - 615

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 4

ER -