Phosphorus MRS was evaluated as a monitor of tumour therapeutic response to the herpes simplex virus thymidine kinase suicide gene therapy paradigm. In vivo 31P spectra were obtained from subcutaneous rat C6 gliomas constitutively expressing the HSVtk gene post treatment with ganciclovir (GCV, 15 mg/kg i.p., twice-daily). Significant regression (p < 0.1) of tumour volume was observed 10 days after beginning GCV administration. However, no changes in tumour pH or energy metabolites from pre-treatment values were observed. High-resolution 31P spectra of tumour extracts revealed a statistically significant reduction in the phosphocholine to phosphoethanolamine ratio six days post-GCV administration. These results indicate that the HSVtk/GCV-induced killing of tumours is not associated with corresponding changes in 31P MRS-observable energy metabolites and pH. The observed reduction in the PE/PC ratio may provide a non-invasive in vivo indicator of therapeutic efficacy.

译文

磷MRS被评估为对单纯疱疹病毒胸苷激酶自杀基因治疗范例的肿瘤治疗反应的监测仪。体内31p光谱是从用更昔洛韦治疗后组成性表达HSVtk基因的皮下大鼠C6神经胶质瘤获得的 (GCV,15 mg/kg i.P.,每天两次)。在开始GCV给药10天后观察到肿瘤体积的显著回归 (p <0.1)。然而,未观察到肿瘤pH或能量代谢物与治疗前值的变化。肿瘤提取物的高分辨率31p光谱显示,GCV给药六天后,磷酸胆碱与磷酸乙醇胺的比率在统计学上显着降低。这些结果表明,HSVtk/GCV诱导的肿瘤杀伤与31P MRS可观察到的能量代谢产物和pH的相应变化无关。观察到的PE/PC比率的降低可能提供治疗功效的非侵入性体内指标。

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