Fluorophore-Metallic Colloid Conjugates for Medical Imag

描述(由申请人提供)： 该实验室最近的研究表明，银金属颗粒可以产生戏剧性的有利效应或附近的荧光团。这些效应包括增加量子产率、多光子激发、光稳定吸收截面和更长的荧光共振能量转移距离。这些研究是在银岛薄膜上进行的，在这些薄膜中，银被结合到惰性衬底上。此表格不适用于需要注射的医疗应用程序。我们现在建议开发吲哚青绿(ICG)与银、金或其他贵金属胶体的络合物，用于改善视网膜血管造影和心脏血管成像的光学对比剂。 第一阶段的具体目标和里程碑是： 具体目标1：开发ICG和银胶的络合物的悬浮液，其ICG强度增加10倍，而不增加ICG的整体浓度。 具体目的2：将ICG-胶体复合体用于兔视网膜成像，使ICG强度增加3倍，对兔无急性毒性反应。 该项目的第二阶段将利用第一阶段的经验和结果来指导这一新类别造影剂的进一步开发。 具体目标1：通过控制ICG与金属的距离、偶联化学、惰性涂层的使用和颗粒大小来优化ICG-银络合物的光谱性质。 具体目标2：评估其他金属胶体的使用，包括金、铂和钯 具体目标3：评价ICG胶体在兔眼模型中的应用，以改善脉络膜循环的成像和区分成像。 具体目标4：扩大ICG-金属胶体复合体在心脏血管成像中的应用。

DESCRIPTION (provided by applicant): Recent studies in this laboratory have shown that silver metallic particles can have dramatic favorable effects or nearby fluorophores. These effects include increased quantum yields, multi-photon excitation, photostability absorption cross sections and longer distances for fluorescence resonance energy transfer. These studies were performed on silver island films in which the silver is bound to an inert substrate. This form is not suitable for medical applications requiring injection. We now propose to develop complexes of indocyanine green (ICG)with silver, gold or other nobel metal colloids for use as improved optical contrast agents for retinal angiography and imaging of cardiac vasculature. The Specific Aims and Milestones for Phase I are: Specific Aim 1: Develop suspensions which are complexes of ICG and silver colloids which display a 10-fold increase in ICG intensity without increases in the bulk ICG concentration. Specific Aim 2: Use the ICG-colloid complexes for retinal imaging in rabbits to obtain a 3-fold increase in ICG intensity, without acute toxic effects for the rabbits. Phase II of the project will use the experience and results of Phase I to guide further development of this new class of contrast agents. Specific Aim 1: Optimize the spectral properties of the ICG-silver complexes by controlling the ICG-to-metal distance, coupling chemistry, use of inert coating and particle size. Specific Aim 2: Evaluate the use of other metallic colloids including gold, platinum and palladium Specific Aim 3: Evaluate the use of the ICG-colloids in the rabbit eye model for improved imaging and differential imaging of choroid circulation. Specific Aim 4: Extend the use of ICG-metal colloid complexes for imaging of cardiac vasculature.