In vivo measurement and imaging of tumor oxygenation using coembedded paramagnetic particulates
In vivo measurement and imaging of tumor oxygenation using coembedded paramagnetic particulates
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DOI：
10.1002/mrm.20188
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发表时间：
2004-09-01
影响因子：
3.3
通讯作者：
Kuppusamy, P
中科院分区：
文献类型：
--
作者：
Ilangovan, G;Bratasz, A;Kuppusamy, P
肿瘤组织氧合是一个重要的参数，与某些肿瘤的化疗或放疗结果呈正相关。因此，准确和无创地测定肿瘤中氧（pO(2)）浓度的方法将是有价值的。在这项研究中，利用酞菁锂（LiPc）微晶颗粒的电子顺磁共振（EPR）光谱，对pO(2)作为肿瘤生长函数进行了重复测量。在小鼠接种过程中，我们通过将颗粒与RIF-1肿瘤细胞共植入，将颗粒永久嵌入肿瘤中。这种方法可以在肿瘤生长阶段的50 ~ 2周内反复测量肿瘤中的氧浓度。颗粒稳定，对肿瘤细胞无毒。C3H小鼠体外克隆实验和体内肿瘤生长速率检测均未发现对细胞增殖和肿瘤生长速率有明显影响。结果表明，随着肿瘤的生长，肿瘤的pO(2)呈指数下降，并在接种肿瘤细胞后4天内达到低氧水平（约为4 mmHg）。空间EPR成像显示，包埋颗粒分布不均匀，主要集中在肿瘤体积的中部。通过光谱EPR成像获得肿瘤的氧定位，显示肿瘤内pO(2)的显著变化。总之，EPR光谱和嵌入氧饱和度探针的成像能够在无干扰条件下准确和重复地测量生长肿瘤中的pO(2)。(C) 2004 Wiley-Liss, Inc。
Tumor tissue oxygenation is an important parameter that is positively correlated to the chemo- or radiation treatment outcome of certain tumors. Hence, methods to accurately and noninvasively determine the concentration of oxygen (pO(2)) in tumors will be valuable. In this study, electron paramagnetic resonance (EPR) spectroscopy, utilizing microcrystalline particulates of lithium phthalocyanine (LiPc), was used to perform repeated measurements of pO(2) as a function of tumor growth. We permanently embedded the particulates in the tumor by coimplanting them with RIF-1 tumor cells during inoculation in mice. This procedure enabled repeated measurements of oxygen concentration in the tumor to be obtained for >2 weeks during its growth phase. The particulates were stable and nontoxic to the tumor cells. Both an in vitro clonogenic assay and an in vivo tumor growth rate examination in C3H mice showed no apparent effect on cell proliferation or tumor growth rate. The measurements indicated that the pO(2) of the tumor decreased exponentially with tumor growth and reached hypoxic levels (similar to4 mmHg) within 4 days after inoculation of the tumor cells. Spatial EPR imaging revealed a nonuniform distribution of the embedded particulates, which were localized mainly in the middle of the tumor volume. Oxygen mapping of the tumor, obtained by spectroscopic EPR imaging, showed significant variation of pO(2) within the tumor. In summary, EPR spectroscopy and imaging with an embedded oximetry probe enabled accurate and repeated measurements of pO(2) to be obtained in growing tumors under nonperturbing conditions. (C) 2004 Wiley-Liss, Inc.