Evaluation of magnetonanoparticles conjugated with new angiogenesis peptides in intracranial glioma tumors by MRI

Abstract

Angiogenesis plays a critical role in progression of malignant gliomas. The development of glioma-specific labeling molecules that can aid detection and visualization of angiogenesis can help surgical planning and improve treatment outcome. The aim of this study was to evaluate if two peptides (GX1 and RGD-GX1) linked to angiogenesis can be used as an MR-imaging markers of angiogenesis. MR imaging was performed in U87 glioblastoma-bearing NOD-SCID mice at different time points between 15 and 120 min post-injection to visualize particle distribution. GX1 and RGD-GX1 exhibited the highest accumulation in U87 glioblastoma at 120 min post i.v. administration. GX1-conjugated agents lead to higher decrease in transverse relaxation time (T2) (i.e., stronger contrast enhancement) than RGD-GX1-conjugated agents in U87 glioblastoma tumor model. In addition, we tested if U87-IDH1R132 mutated cell line had different pattern of GX1 or RGD-GX1 particle accumulation. Responses in U87-IDH1WT followed a similar pattern with GX1 contrast agents; however, lower contrast enhancement was observed with RGD-GX1 agents. The specific binding of these peptides to human glioblastoma xenograft in the brain was confirmed by magnetic resonance imaging. The contrast enhancement following injection of magnetonanoparticles conjugated to GX1 peptide matched well with CD31 staining and iron staining.