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 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.