Thomas C, Counsell C, Wood P, Adams G
Unité de radiobiologie, laboratoire de RMN, Chilton, Didcot, Royaume-Uni.
Bull Cancer. 1993 Aug;80(8):666-73.
The biological response of some anti-cancer therapeutic agents is probably mediated via the tumour vasculature. A novel approach using 19F NMR spectroscopy in vivo has been developed to directly measure changes in vascular perfusion volume in experimental tumours. A 100% w/v perfluorooctylebromide (PFOB) emulsion was used as a tracer. For a fixed position of a 7 mm surface coil placed over the tumour, the signal from the PFOB rapidly reached an equilibrium value remaining unchanged for at least 2 hours. Since the strength of the fluorine signal is directly proportional to the perfusion volume of the tumour vasculature, reduction of signal intensity should correspond directly to any reduction in volume which may be a manifestation of a change in the tumour blood flow. This hypothesis was investigated using hydralazine as a physiological modifier of tumour blood flow. Administration of 5 mg/kg of hydralazine following dosing with the PFOB emulsion reduced the 19F signal intensity from the murine tumors RIF-1 and KHT and from the human tumour HT29 with no or little reduction in the SCCVII/Ha murine and HX118 human tumours. Changes in blood volume in KHT tumour accompanied local changes in tumour blood flow rate as measured by the Xe-133 clearance rate technique. Thus, these data demonstrate the potential of the PFOB emulsion as a 19F NMR tracer of the vasculature to measure changes induced by therapeutic agents on blood volume in accessible tumours. This method may also be useful to detect early changes in blood volume produced during angiogenesis of solid tumours or angiostatic activity of anti-cancer drugs.
一些抗癌治疗药物的生物学反应可能是通过肿瘤血管系统介导的。一种利用体内19F核磁共振波谱的新方法已被开发出来,用于直接测量实验性肿瘤中血管灌注体积的变化。100%重量/体积的全氟辛基溴化物(PFOB)乳剂被用作示踪剂。对于放置在肿瘤上方的7毫米表面线圈的固定位置,来自PFOB的信号迅速达到一个平衡值,并在至少2小时内保持不变。由于氟信号的强度与肿瘤血管系统的灌注体积直接成正比,信号强度的降低应直接对应于体积的任何减少,这可能是肿瘤血流变化的一种表现。使用肼作为肿瘤血流的生理调节剂对这一假设进行了研究。在给予PFOB乳剂后,注射5毫克/千克的肼可降低小鼠肿瘤RIF-1和KHT以及人肿瘤HT29的19F信号强度,而SCCVII/Ha小鼠肿瘤和HX118人肿瘤的信号强度则没有或仅有少量降低。KHT肿瘤中的血容量变化伴随着通过Xe-133清除率技术测量的肿瘤血流速度的局部变化。因此,这些数据证明了PFOB乳剂作为血管系统的19F核磁共振示踪剂,用于测量治疗药物对可及肿瘤血容量诱导变化的潜力。这种方法也可能有助于检测实体肿瘤血管生成过程中或抗癌药物的血管生成抑制活性期间产生的血容量早期变化。