de Oliveira Erica Aparecida, Lazovic Jelena, Guo Lea, Soto Horacio, Faintuch Bluma Linkowski, Akhtari Massoud, Pope Whitney
Radiopharmacy Center, Institute of Energy and Nuclear Research, Av. Prof. Lineu Prestes 2242, São Paulo, SP, 05508-000, Brazil.
School of Pharmaceutical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 580 Bloco 17, São Paulo, SP, 05508-900, Brazil.
Appl Biochem Biotechnol. 2017 Sep;183(1):265-279. doi: 10.1007/s12010-017-2443-2. Epub 2017 Mar 9.
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 (T ) (i.e., stronger contrast enhancement) than RGD-GX1-conjugated agents in U87 glioblastoma tumor model. In addition, we tested if U87-IDH1 mutated cell line had different pattern of GX1 or RGD-GX1 particle accumulation. Responses in U87-IDH1 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.
血管生成在恶性胶质瘤的进展中起着关键作用。开发能够辅助检测和可视化血管生成的胶质瘤特异性标记分子有助于手术规划并改善治疗效果。本研究的目的是评估与血管生成相关的两种肽（GX1和RGD-GX1）是否可作为血管生成的磁共振成像标记物。在注射后15至120分钟的不同时间点，对携带U87胶质母细胞瘤的NOD-SCID小鼠进行磁共振成像，以观察颗粒分布。静脉注射后120分钟，GX1和RGD-GX1在U87胶质母细胞瘤中积累最多。在U87胶质母细胞瘤肿瘤模型中，与GX1偶联的试剂比与RGD-GX1偶联的试剂导致横向弛豫时间（T）下降更大（即更强的对比增强）。此外，我们测试了U87-IDH1突变细胞系是否具有不同的GX1或RGD-GX1颗粒积累模式。U87-IDH1对GX1造影剂的反应遵循相似模式；然而，RGD-GX1试剂的对比增强较低。磁共振成像证实了这些肽与脑内人胶质母细胞瘤异种移植物的特异性结合。注射与GX1肽偶联的磁性纳米颗粒后的对比增强与CD31染色和铁染色匹配良好。
