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首页> 外文期刊>International Journal of Biomedical Science >Feasibility Evaluation of Detecting Hydroxymethylphosphine Oxide In Vivo by 31P-MRS
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Feasibility Evaluation of Detecting Hydroxymethylphosphine Oxide In Vivo by 31P-MRS

机译：31P-MRS检测体内羟甲基氧化膦的可行性评估

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Application of organophosphorus compounds in biomedicine is attractive because the 31P nucleus is very amenable to study by nuclear magnetic resonance (NMR) techniques, particularly, by in vivo 31P magnetic resonance spectroscopy (31P-MRS). The water-soluble organophosphorus compounds that are non-toxic, exhibit metabolic stability, and show a unique resonance peak in 31P NMR spectroscopy, which could be ideal to be used as probes for 31P-MRS. Here we evaluated the in vivo feasibility of potentially using a hydroxymethylphosphine oxide as a novel probe for 31P-MRS studies using tris(hydroxymethyl)phosphine oxide (THPO) as an example. THPO was synthesized, injected in the normal CF1 mice, and 31P spectra were acquired before and after injection with the coil located on the regions of interest. The NMR signal from the region of interest appeared within one minute of THPO injection. The compound was stable in vivo as no metabolites of THPO were observed. No toxicity was observed after THPO injection in mice. The peak concentrations of THPO in liver and kidney were reached within 15 min and 60 min respectively. THPO was excreted exclusively in urine without undergoing any metabolism indicating that it is very stable under in vivo conditions. These initial studies in normal CF1 mice clearly demonstrate that THPO possess the essential characteristics required for a potential MRS probe. Based on the current preliminary results, we suggest that HMPs, when incorporated into targeted drugs (peptides, proteins, antibodies, etc.), may serve as novel 31P probes for monitoring the drug distribution in vivo by MRS.
机译：有机磷化合物在生物医学中的应用很有吸引力，因为31P核非常适合通过核磁共振（NMR）技术进行研究，尤其是通过体内31P磁共振波谱（31P-MRS）研究。水溶性有机磷化合物无毒，具有代谢稳定性，并在31P NMR光谱中显示出独特的共振峰，可以理想地用作31P-MRS的探针。在这里，我们评估了潜在的体内可行性，即使用羟甲基氧化膦作为新型探针进行31P-MRS研究，以三（羟甲基）氧化膦（THPO）为例。合成了THPO，注射到正常的CF1小鼠中，在线圈位于目标区域之前和之后获得了31P光谱。 THPO注射后一分钟内出现了来自感兴趣区域的NMR信号。该化合物在体内是稳定的，因为未观察到THPO的代谢产物。在小鼠中注射THPO后未观察到毒性。肝脏和肾脏中THPO的峰值浓度分别在15分钟和60分钟内达到。 THPO仅在尿液中排泄，没有任何新陈代谢，表明它在体内条件下非常稳定。这些在正常CF1小鼠中的初步研究清楚地表明，THPO具有潜在MRS探针所需的基本特征。根据当前的初步结果，我们建议将HMPs掺入靶向药物（肽，蛋白质，抗体等）后，可作为新型31P探针，用于通过MRS监测体内药物分布。

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