State Key Laboratory of Magnetic Resonance and Molecular and Atomic Physics, Wuhan Institute of Physics and Mathematics, The Chinese Academy of Sciences, Wuhan 430071, China.
Contrast Media Mol Imaging. 2010 Jul-Aug;5(4):223-30. doi: 10.1002/cmmi.381.
Fluorescein- and terbium-labelled tuftsin (Thr-Lys-Pro-Arg) and pentapeptide (Thr-Lys-Pro-Pro-Arg) were synthesized and their properties were evaluated in vitro by luminescence spectrometry and confocal microscopy as fluorescence probes to target macrophage cells in biological systems. An increase in fluorescence of macrophages incubated with varying concentrations of fluorescein isothiocyanate or Tb-DOTA-tuftsin/pentapeptide conjugates was observed in a concentration-dependent manner. Tb-DOTA-pentapeptide had a greater affinity to macrophages than Tb-DOTA-tuftsin. Lipopolysaccharide (LPS) stimulation strengthened the internalization of peptide conjugates by macrophages through the tuftsin receptor mechanism. Tb-DOTA-tuftsin/pentapeptide conjugates are likely to be a promising optical reagents as probes of the immune response with involvement of macrophage cells in a variety of diseases. Gd-DOTA-tuftsin conjugate was also evaluated as a cell-specific contrast agent in in vitro MRI experiments. In this context, the macrophages labelled by Gd-DOTA-tuftsin were highly magnetic and detectable by MRI, which confirms that this vectorized MRI probe has the potential to image macrophage-mediated inflammation in diseases like brain traumas and stroke. Tuftsin receptor-specific biological-function domain may have a modified in vivo biodistribution profile, bioavailability and pharmacokinetics subsequent to its conjugation to a metal ion-binding backbone.
荧光素和铽标记的苏氨酸-赖氨酸-脯氨酸-精氨酸（Tuftsin）和五肽（Thr-Lys-Pro-Pro-Arg）被合成，并通过发光光谱法和共聚焦显微镜评估其在生物系统中作为荧光探针靶向巨噬细胞的性质。用不同浓度的异硫氰酸荧光素或 Tb-DOTA-Tuftsin/五肽缀合物孵育的巨噬细胞的荧光强度呈浓度依赖性增加。与 Tb-DOTA-Tuftsin 相比，Tb-DOTA-五肽对巨噬细胞具有更高的亲和力。脂多糖（LPS）刺激通过 Tuftsin 受体机制增强了肽缀合物被巨噬细胞内化。Tb-DOTA-Tuftsin/五肽缀合物有望成为具有前景的光学试剂，可作为涉及多种疾病中巨噬细胞的免疫反应的探针。在体外 MRI 实验中，还评估了 Gd-DOTA-Tuftsin 缀合物作为细胞特异性对比剂。在这种情况下，用 Gd-DOTA-Tuftsin 标记的巨噬细胞具有很强的磁性，可通过 MRI 检测到，这证实了这种载体化的 MRI 探针具有在脑损伤和中风等疾病中成像巨噬细胞介导的炎症的潜力。Tuftsin 受体特异性生物功能域在与金属离子结合的骨架缀合后，可能具有修饰的体内生物分布特征、生物利用度和药代动力学。
