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, Michael H.
AU - van Vuurden, Dannis G.
AU - Kaspers, Gertjan J.L.
AU - Hulleman, Esther
AU - Bugiani, Marianna
N1 - Publisher Copyright:
� Copyright 2018 SNMMI; all rights reserved.
PY - 2018/4
Y1 - 2018/4
N2 - Inadequate tumor uptake of the vascular endothelial growth factor antibody bevacizumab could explain lack of effect in diffuse intrinsic pontine glioma. Methods: By combining data from a PET imaging study using 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 diffuse intrinsic pontine glioma patient was performed. Results: In vivo 89Zr-bevacizumab measurements showed heterogeneity between lesions. Additional ex vivo measurements and immunohistochemistry of cervicomedullary metastasis samples showed uptake to be highest in the area with marked microvascular proliferation. In the primary pontine tumor, all samples showed similar vascular morphology. Other histologic features were similar between the samples studied. Conclusion: In vivo 89Zr-bevacizumab PET serves to identify heterogeneous uptake between tumor lesions, whereas subcentimeter intralesional heterogeneity could be identified only by ex vivo measurements. 89Zr-bevacizumab uptake is enhanced by vascular proliferation, although our results suggest it is not the only determinant of intralesional uptake heterogeneity.
AB - Inadequate tumor uptake of the vascular endothelial growth factor antibody bevacizumab could explain lack of effect in diffuse intrinsic pontine glioma. Methods: By combining data from a PET imaging study using 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 diffuse intrinsic pontine glioma patient was performed. Results: In vivo 89Zr-bevacizumab measurements showed heterogeneity between lesions. Additional ex vivo measurements and immunohistochemistry of cervicomedullary metastasis samples showed uptake to be highest in the area with marked microvascular proliferation. In the primary pontine tumor, all samples showed similar vascular morphology. Other histologic features were similar between the samples studied. Conclusion: In vivo 89Zr-bevacizumab PET serves to identify heterogeneous uptake between tumor lesions, whereas subcentimeter intralesional heterogeneity could be identified only by ex vivo measurements. 89Zr-bevacizumab uptake is enhanced by vascular proliferation, although our results suggest it is not the only determinant of intralesional uptake heterogeneity.
KW - 89Zr-bevacizumab
KW - Brain stem neoplasm
KW - Microvascular morphology
KW - PET
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=85044786797&partnerID=8YFLogxK
U2 - 10.2967/jnumed.117.197897
DO - 10.2967/jnumed.117.197897
M3 - Article
SN - 0161-5505
VL - 59
SP - 612
EP - 615
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 4
ER -