Suzuki Yoshikazu, Iida Mitsuru, Miura Iwao, Inubushi Toshiro, Morikawa Shigehiro
Diagnostic Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Tokushima, Japan.
Pharmaceutical Division, Otsuka Pharmaceutical Co., Ltd., Tokushima, Tokushima, Japan.
PLoS One. 2014 Jul 9;9(7):e102132. doi: 10.1371/journal.pone.0102132. eCollection 2014.
Morphological imaging precedes lesion-specific visualization in magnetic resonance imaging (MRI) because of the superior ability of this technique to depict tissue morphology with excellent spatial and temporal resolutions. To achieve lesion-specific visualization of tumors by MRI, we investigated the availability of a novel polymer-based tracer. Although the 13C nucleus is a candidate for a detection nucleus because of its low background signal in the body, the low magnetic resonance sensitivity of the nucleus needs to be resolved before developing a 13C-based tracer. In order to overcome this problem, we enriched polyethylene glycol (PEG), a biocompatible polymer, with 13C atoms. 13C-PEG40,000 (13C-PEG with an average molecular weight of 40 kDa) emitted a single 13C signal with a high signal-to-noise ratio due to its ability to maintain signal sharpness, as was confirmed by in vivo investigation, and displayed a chemical shift sufficiently distinct from that of endogenous fat. 13C-PEG40,000 intravenously injected into mice showed long retention in circulation, leading to its effective accumulation in tumors reflecting the well-known phenomenon that macromolecules accumulate in tumors because of leaky tumor capillaries. These properties of 13C-PEG40,000 allowed visualization of tumors in mice by 13C spectroscopic imaging. These findings suggest that a technique based on 13C-PEG is a promising strategy for tumor detection.
在磁共振成像（MRI）中，形态学成像先于病变特异性可视化，因为该技术具有卓越的能力，能够以出色的空间和时间分辨率描绘组织形态。为了通过MRI实现肿瘤的病变特异性可视化，我们研究了一种新型聚合物基示踪剂的可用性。尽管13C核因其在体内的低背景信号而成为检测核的候选者，但在开发基于13C的示踪剂之前，需要解决该核的低磁共振灵敏度问题。为了克服这个问题，我们用13C原子富集了生物相容性聚合物聚乙二醇（PEG）。13C-PEG40,000（平均分子量为40 kDa的13C-PEG）由于能够保持信号清晰度，发出了具有高信噪比的单一13C信号，这一点已通过体内研究得到证实，并且其化学位移与内源性脂肪的化学位移有足够明显的差异。静脉注射到小鼠体内的13C-PEG40,000在循环中保留时间长，导致其在肿瘤中有效积累，这反映了众所周知的现象，即由于肿瘤毛细血管渗漏，大分子会在肿瘤中积累。13C-PEG40,000的这些特性使得通过13C光谱成像能够在小鼠体内可视化肿瘤。这些发现表明，基于13C-PEG的技术是一种有前景的肿瘤检测策略。
