EPR Oximetry Sensor-Developing a TAM Derivative for In Vivo Studies.
EPR Oximetry Sensor-Developing a TAM Derivative for In Vivo Studies.
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DOI：
10.1007/s12013-017-0824-3
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发表时间：
2018-06
影响因子：
2.6
通讯作者：
Tadyszak K
中科院分区：
文献类型：
--
作者：
Boś-Liedke A;Walawender M;Woźniak A;Flak D;Gapiński J;Jurga S;Kucińska M;Plewiński A;Murias M;Elewa M;Lampp L;Imming P;Tadyszak K
氧合作用是生物系统最重要的生理参数之一。低氧浓度(低氧)与不同器官的各种病理生理过程有关。缺氧在肿瘤治疗中具有特殊的重要性，导致治疗反应不佳。三芳基甲基()衍生物是电子顺磁共振中常用的传感器，用于定量的组织氧定位。它们也被称为磁共振成像(MRI)造影剂和荧光成像化合物。我们报道了自由基tris(2，3，5，6-tetrachloro-4-carboxy-phenyl)methyl，(PtMTC)的性质，它是一种潜在的多峰(EPR/荧光)标记。用电子顺磁共振对其进行光谱分析，评价其对适宜静脉注射的液体环境(1 mm PbS，pH = 7.4)的敏感性。此外，用相同的溶剂测量了自由基的荧光发射，并估算了它的量子产率。对两种癌细胞株HT-29(结直肠腺癌)和FaDu(鳞癌)进行了体外细胞毒性试验和摄取试验。测定了自由基在不同溶液(PBS、pH、 = 、HT-29和FADu细胞培养及细胞毒)、大鼠全血和血浆中的稳定性。最后对PTMTC进行了初步的小鼠毒性试验。光谱研究结果证实了PTMTC的多峰特性。PTMTC被证明不被癌细胞吸收，也不干扰基于荧光素-荧光素酶的检测。体外和体内试验也表明，它是无毒的，可以自由地给药，直到250 mg/kg bw通过两个静脉注射。和IP。打针。这项工作表明，PTMTC是临床前研究中理想的多模式(EPR/荧光)造影剂。
Oxygenation is one of the most important physiological parameters of biological systems. Low oxygen concentration (hypoxia) is associated with various pathophysiological processes in different organs. Hypoxia is of special importance in tumor therapy, causing poor response to treatment. Triaryl methyl (TAM) derivative radicals are commonly used in electron paramagnetic resonance (EPR) as sensors for quantitative spatial tissue oxygen mapping. They are also known as magnetic resonance imaging (MRI) contrast agents and fluorescence imaging compounds. We report the properties of the TAM radical tris(2,3,5,6-tetrachloro-4-carboxy-phenyl)methyl, (PTMTC), a potential multimodal (EPR/fluorescence) marker. PTMTC was spectrally analyzed using EPR and characterized by estimation of its sensitivity to the oxygen in liquid environment suitable for intravenous injection (1 mM PBS, pH = 7.4). Further, fluorescent emission of the radical was measured using the same solvent and its quantum yield was estimated. An in vitro cytotoxicity examination was conducted in two cancer cell lines, HT-29 (colorectal adenocarcinoma) and FaDu (squamous cell carcinoma) and followed by uptake studies. The stability of the radical in different solutions (PBS pH = 7.4, cell media used for HT-29 and FaDu cells culturing and cytotoxicity procedure, full rat blood and blood plasma) was determined. Finally, a primary toxicity test of PTMTC was carried out in mice. Results of spectral studies confirmed the multimodal properties of PTMTC. PTMTC was demonstrated to be not absorbed by cancer cells and did not interfere with luciferin-luciferase based assays. Also in vitro and in vivo tests showed that it was non-toxic and can be freely administrated till doses of 250 mg/kg BW via both i.v. and i.p. injections. This work illustrated that PTMTC is a perfect candidate for multimodal (EPR/fluorescence) contrast agent in preclinical studies.
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影响因子：
2.8
作者：
Augustyniak-Jablokow, Maria A.;Tadyszak, Krzysztof;Lijewski, Stefan
通讯作者：
Lijewski, Stefan
影响因子：
6.7
作者：
Nathan, AT;Singer, M
通讯作者：
Singer, M
影响因子：
9.7
作者：
Mikula-Pietrasik, Justyna;Sosinska, Patrycja;Ksiazek, Krzysztof
通讯作者：
Ksiazek, Krzysztof
DOI：
10.1073/pnas.042671399
发表时间：
2002-02-19
影响因子：
11.1
作者：
Krishna, MC;English, S;Mitchell, JB
通讯作者：
Mitchell, JB
影响因子：
2.2
作者：
Qiao, Zhiwei;Redler, Gage;Halpern, Howard
通讯作者：
Halpern, Howard