A LECTIN-CONTRAST AGENT FOR MULTIMODALITY MOLECULAR IMAGING OF TUMOR ANGIOGENESIS

用于肿瘤血管生成多模式分子成像的凝集素造影剂

• 批准号: 7470274
• 负责人: Arvind P Pathak
• 金额: $ 22.14万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7470274
• 关键词: Affect; Affinity; Architecture; Binding; Biodistribution; Blood Circulation; Blood Vessels; Breast Cancer Model; Confocal Microscopy; Contrast Media; Data; Endothelial Cells; Fluorescein-5-isothiocyanate; Gadolinium; Gadolinium DTPA; Gadopentetate Dimeglumine; Goals; Griffonia simplicifolia lectins; Half-Life; Human; Image; Immune; In Vitro; Label; Laser Scanning Confocal Microscopy; Lectin; Liposomes; Magnetic Resonance Imaging; Methods; Microscopy; Modality; Molecular; Monitor; Multimodal Imaging; Nanosphere; Neoplasms in Vascular Tissue; Optics; Patients; Perfusion; Proteins; Range; Rate; Relaxation; Resolution; Role; Specificity; Time; Tissues; Toxic effect; Tumor Angiogenesis; Validation; Vascular remodeling; Xenograft Model; angiogenesis; base; carbohydrate binding protein; digital; fluorophore; imaging probe; improved; in vivo; malignant breast neoplasm; molecular imaging; nanoparticle; novel; receptor; tool; tumor; tumor progression

DESCRIPTION (provided by applicant): The primary goal of this proposal is to develop a de novo lectin-targeted imaging probe that improves our ability to image the structural and functional changes in tumor blood vessels during angiogenesis, using molecular magnetic resonance imaging (MRI). We propose to develop a dual-modality (MRI and optical) contrast agent targeted to the lumen of blood vessels using the lectin from Bandeiraea Simplicifolia (GS-1), a protein of non-immune origin that binds to endothelial cells, for up to 18h in vivo without extravasating from tumor vessels. Aim 1 is focused on developing a T1 liposome-based lectin-targeted contrast agent, while Aim 2 focuses on developing a T2 superparamagnetic lectin-targeted nanoparticle based contrast agent. With these new contrast agents, we intend to characterize the remodeling of the vascular architecture that accompanies tumor progression, in a human metastatic breast cancer model. We will do this in vivo using high-resolution 3D MRI, and for the first time ex vivo using MR microscopy (}MRI), producing the very first 3D }digital casts} of the vessel architecture. The fluorescent tag on these new contrast agents will enable direct validation of the MRI data with laser scanning confocal microscopy. These data will promote our understanding of the basic mechanisms underlying angiogenesis and resulting image contrast. Its low toxicity, blood vessel specificity and extensive half-life in vivo, could make our lectin-targeted contrast agents an invaluable new tool for monitoring the efficacy of anti-angiogenic therapies in patients. The application titled "A Lectin-Contrast Agent For Multimodality Molecular Imaging of Tumor Angiogenesis" is centered on developing a novel lectin-based contrast agent for molecular MRI, which preferentially targets blood vessels via the affinity of the lectin from Bandeiraea Simplicifolia for endothelial cells. We intend to synthesize and characterize, both T1 and T2 versions of this contrast agent, and employ them to better understand the role of tumor angiogenesis in a human metastatic breast cancer xenograft model.

描述（由申请人提供）：该提案的主要目标是开发以凝集素为目标的成像探针，以提高我们使用分子磁共振成像（MRI）在血管生成期间在血管生成过程中成像肿瘤血管中结构和功能变化的能力。我们建议使用Bandeiraea SimpliCifolia（GS-1）的凝集素（GS-1）的凝集素（一种与内皮细胞结合的蛋白质，一种与内皮细胞结合的蛋白质，在无肿瘤容器中至最高18H的非免疫起源的蛋白质（GS-1），该双模式（MRI和光学）对比剂（MRI和光学）对比剂，该剂量是血管的腔。 AIM 1的重点是开发以T1脂质体为基础的凝集素靶向对比剂，而AIM 2专注于开发基于T2的超级磁性凝集素靶向纳米颗粒的对比剂。使用这些新的对比剂，我们打算在人类转移性乳腺癌模型中表征伴随肿瘤进展的血管结构的重塑。我们将使用高分辨率3D MRI进行体内进行此操作，并首次使用MR显微镜（} MRI）进行离体，从而产生容器架构的第一个3D}数字铸造}。这些新的对比剂上的荧光标签将通过激光扫描共聚焦显微镜直接验证MRI数据。这些数据将促进我们对血管生成和产生图像对比的基本机制的理解。它的低毒性，血管特异性和体内丰富的半衰期可能使我们的凝集素靶向对比剂成为监测患者抗血管生成疗法功效的宝贵新工具。该应用标题为“用于肿瘤血管生成的多模态分子成像的凝集素 - 对比剂”，集中在为分子MRI开发一种新型的基于凝集素的对比剂，该对比剂通过bandeiraea simplecifolia for bandeirairae simplicifolia of bandeiraia simplectife of to to剂。我们打算合成和表征该对比剂的T1和T2版本，并利用它们更好地了解肿瘤血管生成在人类转移性乳腺癌异种移植模型中的作用。