Constantinidis I, Gamcsik M P
Frederik Philips Magnetic Resonance Research Center, Department of Radiology, Emory University, Atlanta, GA 30322, USA.
Int J Radiat Oncol Biol Phys. 1995 Aug 30;33(1):143-9. doi: 10.1016/0360-3016(94)00658-8.
Previous studies from our laboratory have suggested that pooling of ammonium in tumor tissues may be caused by its inefficient removal due to the poor vasculature commonly found in tumors. The purpose of these experiments was to validate the relationship between tumor ammonium ion concentration and tumor blood flow, and to determine whether large concentrations of ammonium ion detected by Nuclear Magnetic Resonance (NMR) spectroscopy are either produced within the tumor or simply imported into the tumor through the blood stream.
To test this hypothesis, we reduced blood flow in subcutaneously grown Radiation Induced Fibrosarcoma-1 (RIF-1) tumors, either by creating partial ischemia with a bolus injection of hydralazine or by occlusion with surgical sutures. 14N and 31P NMR spectroscopy were used to detect the presence of ammonium, and to assess the bioenergetic status of the tumors, respectively.
A correlation between ammonium ion concentration and PCr/Pi ratio was established for untreated tumors. An increase in the in vivo tumor ammonium ion concentration was observed for every tumor that experienced a reduction in blood flow caused by either hydralazine injection or suture ligation. Changes in ammonium ion concentration paralleled changes in the bioenergetics of hydralazine-treated tumors.
Our results support the hypothesis that a reduction in tumor blood flow is responsible for the accumulation of ammonium in tumors, and that detected ammonium originated from within the tumor.
我们实验室之前的研究表明，肿瘤组织中铵的蓄积可能是由于肿瘤中常见的血管系统不佳导致其清除效率低下所致。这些实验的目的是验证肿瘤铵离子浓度与肿瘤血流之间的关系，并确定通过核磁共振（NMR）光谱检测到的高浓度铵离子是在肿瘤内产生的，还是仅仅通过血流进入肿瘤的。
为了验证这一假设，我们通过大剂量注射肼屈嗪造成局部缺血或用手术缝线结扎来减少皮下生长的辐射诱导纤维肉瘤-1（RIF-1）肿瘤的血流。分别使用14N和31P NMR光谱检测铵的存在，并评估肿瘤的生物能量状态。
在未治疗的肿瘤中建立了铵离子浓度与磷酸肌酸/无机磷酸（PCr/Pi）比值之间的相关性。对于每一个因注射肼屈嗪或缝合结扎导致血流减少的肿瘤，均观察到体内肿瘤铵离子浓度升高。铵离子浓度的变化与肼屈嗪治疗的肿瘤的生物能量变化平行。
我们的结果支持以下假设，即肿瘤血流减少是肿瘤中铵蓄积的原因，且检测到的铵起源于肿瘤内部。
