Pirollo Kathleen F, Dagata John, Wang Paul, Freedman Matthew, Vladar Andras, Fricke Stanley, Ileva Lilia, Zhou Qi, Chang Esther H
Georgetown University Medical Center, Washington, DC 20057-1460, USA.
Mol Imaging. 2006 Jan-Mar;5(1):41-52.
The development of improvements in magnetic resonance imaging (MRI) that would enhance sensitivity, leading to earlier detection of cancer and visualization of metastatic disease, is an area of intense exploration. We have devised a tumor-targeting, liposomal nanodelivery platform for use in gene medicine. This systemically administered nanocomplex has been shown to specifically and efficiently deliver both genes and oligonucleotides to primary and metastatic tumor cells, resulting in significant tumor growth inhibition and even tumor regression. Here we examine the effect on MRI of incorporating conventional MRI contrast agent Magnevist into our anti-transferrin receptor single-chain antibody (TfRscFv) liposomal complex. Both in vitro and in an in vivo orthotopic mouse model of pancreatic cancer, we show increased resolution and image intensity with the complexed Magnevist. Using advanced microscopy techniques (scanning electron microscopy and scanning probe microscopy), we also established that the Magnevist is in fact encapsulated by the liposome in the complex and that the complex still retains its nanodimensional size. These results demonstrate that this TfRscFv-liposome-Magnevist nanocomplex has the potential to become a useful tool in early cancer detection.
提高磁共振成像（MRI）的灵敏度以实现癌症的早期检测和转移病灶的可视化，这一领域正在进行深入探索。我们设计了一种用于基因治疗的肿瘤靶向脂质体纳米递送平台。这种经全身给药的纳米复合物已被证明能够特异性且高效地将基因和寡核苷酸递送至原发性和转移性肿瘤细胞，从而显著抑制肿瘤生长甚至使肿瘤消退。在此，我们研究了将传统MRI造影剂钆喷酸葡胺（Magnevist）掺入我们的抗转铁蛋白受体单链抗体（TfRscFv）脂质体复合物后对MRI的影响。无论是在体外还是在胰腺癌原位小鼠模型中，我们都发现复合了钆喷酸葡胺的复合物具有更高的分辨率和图像强度。使用先进的显微镜技术（扫描电子显微镜和扫描探针显微镜），我们还确定钆喷酸葡胺实际上被复合物中的脂质体包裹，并且该复合物仍保持其纳米尺寸。这些结果表明，这种TfRscFv - 脂质体 - 钆喷酸葡胺纳米复合物有潜力成为早期癌症检测的有用工具。
