Vaupel P, Okunieff P, Neuringer L J
Department of Radiation Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston 02114.
Int J Hyperthermia. 1990 Jan-Feb;6(1):15-31. doi: 10.3109/02656739009140801.
In vivo 31P-NMR spectroscopy was used to monitor the energy metabolism, apparent intracellular pH (pHNMR), and phospholipid turnover in subcutaneous fibrosarcomas (FSall) and mammary carcinomas (MCaIV) treated with hyperthermia (HT). Treatment consisted of elevation of tumour temperature to 43.5 degrees C for 15, 30 or 60 min (FSall) and 30 min (MCaIV). Experiments were performed on conscious mice with biologically relevant tumour sizes. Using water bath immersion, this study focused on acute heat-induced metabolic changes (up to 7 h post-HT). 31P-NMR spectra of both murine tumours were characterized by relatively high pretreatment levels of PME, Pi and NTP, and lower levels of PDE, PCr and DPDE. Following hyperthermia, NTP and PCr levels, as well as pHNMR, decreased in both tumour lines. This drop was accompanied by a prompt and dramatic increase in Pi. After heating for 15 min, the limited spectral changes observed for the high-energy phosphates and the marginal decline in pHNMR were nullified within 7 h, whereas Pi remained significantly elevated. With the exception of PME/NTP and PME/PDE, all relevant metabolic ratios (PCr/Pi, NTP/Pi, PME/Pi) decreased after heating and did not resolve thereafter. Upon longer heat exposure times the high-energy phosphates, pHNMR, NTP/Pi, PCr/Pi, and PME/Pi all decreased in a dose-dependent manner and remained at the respective lower levels. The PME/PDE ratio was increased after 43.5 degrees C/15 min whereas at longer heating times this ratio did not change. At comparable heat doses MCaIV tumours seem to exhibit changes similar to FSall tumours.
采用体内31P核磁共振波谱法监测经热疗（HT）处理的皮下纤维肉瘤（FSall）和乳腺癌（MCaIV）的能量代谢、表观细胞内pH值（pHNMR）以及磷脂周转率。治疗方法是将肿瘤温度升高至43.5摄氏度，持续15、30或60分钟（FSall）以及30分钟（MCaIV）。实验在具有生物学相关肿瘤大小的清醒小鼠身上进行。通过水浴浸泡，本研究聚焦于急性热诱导的代谢变化（热疗后长达7小时）。两种小鼠肿瘤的31P核磁共振波谱特征为，预处理时PME、Pi和NTP水平相对较高，而PDE、PCr和DPDE水平较低。热疗后，两种肿瘤细胞系中的NTP和PCr水平以及pHNMR均下降。这种下降伴随着Pi的迅速且显著增加。加热15分钟后，高能磷酸盐观察到的有限光谱变化以及pHNMR的轻微下降在7小时内消失，而Pi仍显著升高。除PME/NTP和PME/PDE外，所有相关代谢比率（PCr/Pi、NTP/Pi、PME/Pi）在加热后均下降，且此后未恢复。热暴露时间延长后，高能磷酸盐水平、pHNMR、NTP/Pi、PCr/Pi和PME/Pi均呈剂量依赖性下降，并维持在各自较低水平。43.5摄氏度/15分钟后PME/PDE比率升高，而加热时间更长时该比率不变。在相当的热剂量下，MCaIV肿瘤似乎表现出与FSall肿瘤相似的变化。
