Early MRI findings of targeting the NG2 proteoglycan in GBM

Abstract

Glioblastoma multiforme (GBM) is an aggressive brain tumor where patients have median survival of only 14.6 months. High NG2 expression in GBMs correlates with increased angiogenesis, drug resistance and shorter overall survival. We aimed to target NG2 with monoclonal antibodies (mAb) combined with natural killer (NK) cells in an adoptive immunotherapy approach in athymic rats bearing human GBM. The treatment response was monitored longitudinally using multiparametric MRI including morphological, dynamic contrast enhanced (DCE) and diffusion weighted imaging. The animals were divided into no treatment (n=8), mAb (n=9), NK cells (n=12) and mAb+NK cells (n=8). The overall survival, histological analyses and DCE‐MRI showed that the combined mAb+NK had therapeutic efficacy, where the leakage space (ve) was significantly increased indicating increased cell death. Changes in the microvascular parameters transfer constant (Ktrans) and area under the curve (AUC) were transiently detected in the mAb and NK cell groups. Diffusion values showed no significant change over time. Multiparametric MRI may facilitate individualized therapy by early detection of treatment responses.Support: The Norwegian Cancer Society, Western Norway Regional Health Authority and National Functional Genomics Programme (FUGE) of the Research Council of Norway