PDF(Pubmed)
Abstract：
Current clinical diagnostic imaging methods for lung metastases are sensitive only to large tumours (1-2 mm cross-sectional diameter), and early detection can dramatically improve treatment. We have previously demonstrated that an antibody-targeted MRI contrast agent based on microparticles of iron oxide (MPIO; 1 μm diameter) enables the imaging of endothelial vascular cell adhesion molecule-1 (VCAM-1). Using a mouse model of lung metastasis, upregulation of endothelial VCAM-1 expression was demonstrated in micrometastasis-associated vessels but not in normal lung tissue, and binding of VCAM-MPIO to these vessels was evident histologically. Owing to the lack of proton MRI signals in the lungs, we modified the VCAM-MPIO to include zirconium-89 (89Zr, t1/2 = 78.4 h) in order to allow the in vivo detection of lung metastases by positron emission tomography (PET). Using this new agent (89Zr-DFO-VCAM-MPIO), it was possible to detect the presence of micrometastases within the lung in vivo from ca. 140 μm in diameter. Histological analysis combined with autoradiography confirmed the specific binding of the agent to the VCAM-1 expressing vasculature at the sites of pulmonary micrometastases. By retaining the original VCAM-MPIO as the basis for this new molecular contrast agent, we have created a dual-modality (PET/MRI) agent for the concurrent detection of lung and brain micrometastases.
摘要：
目前肺转移瘤的临床诊断成像方法仅对大肿瘤（横截面直径1-2mm）敏感，早期检测可以显著改善治疗。我们先前已经证明，基于氧化铁微粒（MPIO；1μm直径）的抗体靶向MRI造影剂可以对内皮血管细胞粘附分子-1（VCAM-1）进行成像。使用小鼠肺转移模型，内皮VCAM-1表达上调在微转移相关血管中被证实，但在正常肺组织中没有，VCAM-MPIO与这些血管的结合在组织学上是明显的。由于肺部缺乏质子MRI信号，我们修改了VCAM-MPIO，使其包括锆-89(89Zr，t1/2=78.4h），以便通过正电子发射断层扫描（PET）在体内检测肺转移。使用这个新的代理（89Zr-DFO-VCAM-MPIO），有可能检测到体内肺微转移的存在。直径140μm。组织学分析结合放射自显影证实了该试剂在肺微转移部位与表达VCAM-1的脉管系统的特异性结合。通过保留原始VCAM-MPIO作为这种新分子造影剂的基础，我们创造了一种双模式(PET/MRI)药物,用于同时检测肺和脑微转移.
