Near-infrared-labeled tetracycline derivative is an effective marker of bone deposition in mice
Near-infrared-labeled tetracycline derivative is an effective marker of bone deposition in mice
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DOI：
10.1016/j.ab.2011.05.011
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发表时间：
2011-09-15
影响因子：
2.9
通讯作者：
Olive, D. Michael
中科院分区：
文献类型：
--
作者：
Kovar, Joy L.;Xu, Xinshe;Olive, D. Michael
骨特异性化合物已被有效地用于检测骨矿化、生长和形态学变化。这些试剂通常含有亚氨基二乙酸基团，其可以与磷灰石形成复合物并在可见光谱中发出荧光。我们利用这些化学螯合剂的一个子集来生产用于临床前动物成像的近红外（NIR）光学骨标记物。通过将目标化合物与IRDye 800CW结合，我们将有效的荧光信号检测扩展到NIR区域，而不影响化合物作为矿化过程标记物的能力。钙黄绿素和四环素衍生物（BoneTag试剂[BT]）特异性结合分化的矿化成骨细胞培养物，后者表现出6倍的信号强度。随后的体内试验证明了IRDye 800CW BT的有效骨骼标记。我们能够从（i）在IRDye 680 Bland给药前6周注射IRDye 800CW BT的正常生长小鼠和（ii）比较假治疗和卵巢切除小鼠皮质骨的骨质疏松症小鼠模型中确定骨切片中变化的矿化前沿。这些结果提供了证据表明，近红外标记的BT是有效的骨骼特征的一般标志物和骨矿化和重塑过程的指标。(C)2011 Elsevier Inc. All rights reserved.
Bone-specific compounds have been used effectively for the detection of bone mineralization, growth, and morphological changes. These agents typically contain iminodiacetic acid groups that can form complexes with apatite and fluoresce in the visible spectrum. We exploited a subset of these chemical chelators to produce a near-infrared (NIR) optical bone marker for preclinical animal imaging. By conjugating target compounds to IRDye 800CW, we extended the effective fluorescence signal detection to the NIR region without affecting the compound's ability to function as a marker of the mineralization process. Calcein and a tetracycline derivative (BoneTag agent [BT]) bound specifically to differentiated mineralized osteoblast cultures, with the latter exhibiting 6-fold higher signal intensities. Subsequent in vivo testing demonstrated effective skeletal labeling with IRDye 800CW BT. We were able to identify a changing mineralization front in bone sections from (i) normal growing mice injected with IRDye 800CW BT 6 weeks prior to the administration of IRDye 680 Bland (ii) an osteoporosis mouse model comparing cortical bone in sham-treated and ovariectomized mice. These results provide evidence that the NIR-labeled BT is effective as a general marker of skeletal features and an indicator of the bone mineralization and remodeling processes. (C) 2011 Elsevier Inc. All rights reserved.