Biomedical Magnetic Resonance Unit, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
Contrast Media Mol Imaging. 2010 Sep-Oct;5(5):258-67. doi: 10.1002/cmmi.382.
The aim of the study was to evaluate the ability of a new MR contrast agent to detect cell death as a biomarker of the efficacy of anti-cancer treatment. The phosphatidylserine-targeted hexapeptide (E3) was coupled to pegylated ultrasmall iron oxide nanoparticles (USPIO) that can be detected by magnetic resonance imaging (MRI) and by electron paramagnetic resonance (EPR). USPIO binding to staurosporine-treated TLT (transplantable liver tumor) cells, evaluated by X-Band EPR, indicated twice as much binding of USPIO grafted with the E3 peptide, compared with USPIO grafted with a scrambled peptide or ungrafted USPIO. In vivo experiments were carried out using TLT cells implanted intramuscularly into NMRI mice, and tumor cell death was induced by irradiation. After intravenous injection of the different types of USPIO, the accumulation of contrast agent was evaluated ex vivo by X-band EPR, in vivo by L-band EPR and by T(2)-weighted MRI. In irradiated tumors there was greater accumulation of the targeted USPIO particles compared with control particles or compared with the targeted particles in untreated tissues. In conclusion, phosphatidylserine-targeting of USPIO particles can detect dying tissues. This molecular targeted system should be evaluated further as a potential biomarker of tumor response to treatment.
本研究旨在评估一种新型磁共振对比剂检测细胞死亡的能力，作为评估抗癌治疗效果的生物标志物。该研究将靶向磷脂酰丝氨酸的六肽（E3）与聚乙二醇化超小氧化铁纳米颗粒（USPIO）偶联，通过磁共振成像（MRI）和电子顺磁共振（EPR）进行检测。通过 X 波段 EPR 评估，发现与偶联了乱序肽或未偶联 USPIO 的 USPIO 相比，E3 肽偶联的 USPIO 与 staurosporine 处理的 TLT（移植性肝肿瘤）细胞的结合增加了一倍。在将 TLT 细胞植入 NMRI 小鼠的肌肉内并通过辐照诱导肿瘤细胞死亡的体内实验中，通过 X 波段 EPR 进行了体外评估，通过 L 波段 EPR 和 T2 加权 MRI 进行了体内评估。在辐照的肿瘤中，与对照颗粒或未经处理的组织中的靶向 USPIO 颗粒相比，靶向 USPIO 颗粒的积累更多。总之，靶向 USPIO 颗粒的磷脂酰丝氨酸可以检测到死亡组织。这种分子靶向系统应该进一步评估，作为肿瘤对治疗反应的潜在生物标志物。
