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，银金属颗粒可以对附近的荧光团产生显著的有利影响。这些效应包括增加的量子产率、多光子激发、光稳定性吸收截面和更长的荧光共振能量转移距离。这些研究是在银岛膜上进行的，其中银与惰性基底结合。该形式不适用于需要注射的医疗应用。我们现在提出开发吲哚菁绿色（ICG）与银、金或其它贵金属胶体的复合物，用作视网膜血管造影和心脏血管成像的改进的光学造影剂。 第一阶段的具体目标和任务是： 具体目标1：开发ICG和银胶体复合物的悬浮液，其显示ICG强度增加10倍，而不增加本体ICG浓度。 具体目标二：将ICG-胶体复合物用于兔视网膜成像，可使ICG强度增加3倍，对兔无急性毒性作用。 该项目的第二阶段将使用第一阶段的经验和结果来指导这类新型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、耦合化学、惰性涂层的使用和粒度来优化ICG-银复合物的光谱特性。 具体目标2：评价其他金属胶体（包括金、铂和钯）的使用 具体目的3：评价ICG-胶体在兔眼模型中用于改善脉络膜循环的成像和差异成像的用途。 具体目标4：扩展ICG-金属胶体复合物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.