MRI monitoring of monocytes to detect immune stimulating treatment response in brain tumor

作者：Yang Runze; Sarkar Susobhan; Korchinski Daniel J; Wu Ying; Yong V Wee; Dunn Jeff F^*

来源：Neuro-Oncology, 2017, 19(3): 364-371.

DOI：10.1093/neuonc/now180

• drug response
• glioblastoma
• innate immunity
• iron oxide
• MRI

Background. Glioblastoma (GBM) is an aggressive brain cancer with a poor prognosis. The use of immune therapies to treat GBM has become a promising avenue of research. It was shown that amphotericin B (Amp B) can stimulate the innate immune system and suppress the growth of brain tumor initiating cells (BTICs). However, it is not feasible to use histopathology to determine immune activation in patients. We developed an MRI technique that can rapidly detect a therapeutic response in animals treated with drugs that stimulate innate immunity. Ultrasmall iron oxide nanoparticles (USPIOs) are MRI contrast agents that have been widely used for cell tracking. We hypothesized that the increased monocyte infiltration into brain tumors due to Amp B can be detected using USPIO-MRI, providing an indicator of early drug response.
Methods. We implanted human BTICs into severe combined immunodeficient mice and allowed the tumor to establish before treating the animals with either Amp B or vehicle and then imaged them using MRI with USPIO (ferumoxytol) contrast.
Results. After 7 days of treatment, there was a significantly decreased T-2* in the tumor of Amp B but not vehicle animals, suggesting that USPIO is carried into the tumor by monocytes. We validated our MRI results with histopathology and confirmed that Amp B-treated animals had significantly higher levels of macrophage/microglia that were colocalized with iron staining in their brain tumor compared with vehicle mice.
Conclusion. USPIO-MRI is a promising method of rapidly assessing the efficacy of anticancer drugs that stimulate innate immunity.

• 出版日期2017-3-1