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

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.