In vivo imaging of bone using a deep-red fluorescent molecular probe bearing multiple iminodiacetate groups.
In vivo imaging of bone using a deep-red fluorescent molecular probe bearing multiple iminodiacetate groups.
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DOI：
10.1021/mp400357v
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发表时间：
2013-11-04
影响因子：
4.9
通讯作者：
Smith BD
中科院分区：
文献类型：
--
作者：
Harmatys KM;Cole EL;Smith BD
描述了深红色荧光分子探针，其具有树突状分子结构，具有方酸轮烷核心支架和多个外围亚氨基二乙酸酯基团作为骨靶向单元。亚氨基二乙酸盐的骨亲和力比双膦酸盐低，本研究的主要目标是确定需要多少附加的亚氨基二乙酸盐基团才能对活体啮齿动物的骨进行有效的深红色荧光成像。一系列的体外和体内成像研究表明，四（亚氨基二乙酸）探针染色骨更强烈比类似的双（亚氨基二乙酸）探针。此外，对照四（亚氨基二丙酸酯）探针没有表现出骨靶向能力。四（亚氨基二乙酸）探针靶向与近红外双膦酸盐探针OsteoSense®750相同的高骨转换区域。纵向研究表明，用四（亚氨基二乙酸）探针处理的活小鼠的荧光图像信号在19天内比OsteoSense®750的信号稳定得多。四（亚氨基二乙酸酯）探针的窄发射带使其非常有吸引力，包括在多重成像协议，采用多种荧光探针的混合物在骨生长的临床前研究或荧光引导手术。结果还表明，分子或纳米粒子轴承多价亚氨基二乙酸基团有希望作为骨靶向剂与各种药物应用的可调性能。
Deep-red fluorescent molecular probes are described that have dendritic molecular architecture with a squaraine rotaxane core scaffold and multiple peripheral iminodiacetate groups as the bone targeting units. Iminodiacetates have inherently lower bone affinity than bisphosphonates and a major goal of the study was to determine how many appended iminodiacetate groups are required for effective deep-red fluorescence imaging of bone in living rodents. A series of in vitro and in vivo imaging studies showed that a tetra(iminodiacetate) probe stains bones much more strongly than an analogous bis(iminodiacetate) probe. In addition, a control tetra(iminodiapropionate) probe exhibited no bone targeting ability. The tetra(iminodiacetate) probe targeted the same regions of high bone turnover as the near-infrared bisphosphonate probe OsteoSense®750. Longitudinal studies showed that the fluorescence image signal from living mice treated with the tetra(iminodiacetate) probe was much more stable over 19 days than the signal from OsteoSense®750. The narrow emission band of the tetra(iminodiacetate) probe makes it very attractive for inclusion in multiplex imaging protocols that employ a mixture of multiple fluorescent probes in preclinical studies of bone growth or in fluorescence guided surgery. The results also suggest that molecules or nanoparticles bearing multivalent iminodiacetate groups have promise as bone targeting agents with tunable properties for various pharmaceutical applications.
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