Kline R P, Wu E X, Petrylak D P, Szabolcs M, Alderson P O, Weisfeldt M L, Cannon P, Katz J
Department of Medicine, Columbia University, New York, New York 10032, USA.
Clin Cancer Res. 2000 Jun;6(6):2146-56.
A novel pulse sequence strategy uses sodium magnetic resonance imaging to monitor the response to chemotherapy of mouse xenograft tumors propagated from human prostate cancer cell lines. An inversion pulse suppresses sodium with long longitudinal relaxation times, weighting the image toward intracellular sodium nuclei. Comparing these weighted sodium images before and 24 h after administration of antineoplastics, we measured a 36 +/- 4% (P < 0.001; n = 16) increase in signal intensity. Experiments with these same drugs and cells, treated in culture, detected a significant intracellular sodium elevation (10-20 mM) using a ratiometric fluorescent dye. Flow cytometry studies showed that this elevation preceded cell death by apoptosis, as determined by fluorescent end-labeling of apoptotic nuclei or Annexin V binding. Histopathology on formalin-fixed sections of explanted tumors confirmed that drug administration reduces proliferation (2.2 versus 8.6 mitotic figures per high power field; P < 0.0001), an effect that inversely correlates with the sodium magnetic resonance image response on a tumor-to-tumor basis (P < 0.02; n = 10). Morphological features, such as central zones of nonviable cells, rims of active apoptosis, and areas of viable tumor, could be distinguished by comparing weighted and unweighted images. Advantages of this sodium imaging technique include rapid determination of drug efficacy, improved diagnosis of lesions, ease of coregistration with high resolution proton magnetic resonance imaging, and absence of costly or toxic reagents.
一种新型脉冲序列策略利用钠磁共振成像来监测源自人前列腺癌细胞系的小鼠异种移植肿瘤对化疗的反应。反转脉冲抑制具有长纵向弛豫时间的钠，使图像加权于细胞内钠核。在给予抗肿瘤药物之前和之后24小时比较这些加权钠图像，我们测量到信号强度增加了36±4%（P<0.001；n = 16）。对在培养中用这些相同药物和细胞处理的实验，使用比例荧光染料检测到细胞内钠显著升高（10 - 20 mM）。流式细胞术研究表明，这种升高先于细胞凋亡导致的细胞死亡，这是通过凋亡细胞核的荧光末端标记或膜联蛋白V结合来确定的。对移植肿瘤的福尔马林固定切片进行组织病理学检查证实，给药可降低增殖（每高倍视野有丝分裂数分别为2.2和8.6；P<0.0001），这种效应在肿瘤与肿瘤之间与钠磁共振图像反应呈负相关（P<0.02；n = 10）。通过比较加权和未加权图像可以区分形态学特征，如无活力细胞的中心区域、活跃凋亡边缘和存活肿瘤区域。这种钠成像技术的优点包括快速确定药物疗效、改善病变诊断、易于与高分辨率质子磁共振成像进行配准，以及无需使用昂贵或有毒试剂。
