临床前评估 Gd-DTPA 和 gadomelitol 作为宫颈癌间质液压力 DCE-MRI 的对比剂。
Preclinical evaluation of Gd-DTPA and gadomelitol as contrast agents in DCE-MRI of cervical carcinoma interstitial fluid pressure.
机构信息
Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Nydalen, Box 4953, Oslo N-0424, Norway.
出版信息
BMC Cancer. 2012 Nov 22;12:544. doi: 10.1186/1471-2407-12-544.
BACKGROUND
High interstitial fluid pressure (IFP) in the primary tumor is associated with poor disease-free survival in locally advanced cervical carcinoma. A noninvasive assay is needed to identify cervical cancer patients with highly elevated tumor IFP because these patients may benefit from particularly aggressive treatment. It has been suggested that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as contrast agent may provide useful information on the IFP of cervical carcinomas. In this preclinical study, we investigated whether DCE-MRI with contrast agents with higher molecular weights (MW) than Gd-DTPA would be superior to Gd-DTPA-based DCE-MRI.
METHODS
CK-160 human cervical carcinoma xenografts were subjected to DCE-MRI with Gd-DTPA (MW of 0.55 kDa) or gadomelitol (MW of 6.5 kDa) as contrast agent before tumor IFP was measured invasively with a Millar SPC 320 catheter. The DCE-MRI was carried out at a spatial resolution of 0.23 × 0.23 × 2.0 mm³ and a time resolution of 14 s by using a 1.5-T whole-body scanner and a slotted tube resonator transceiver coil constructed for mice. Parametric images were derived from the DCE-MRI recordings by using the Tofts iso-directional transport model and the Patlak uni-directional transport model.
RESULTS
When gadomelitol was used as contrast agent, significant positive correlations were found between the parameters of both pharmacokinetic models and tumor IFP. On the other hand, significant correlations between DCE-MRI-derived parameters and IFP could not be detected with Gd-DTPA as contrast agent.
CONCLUSION
Gadomelitol is a superior contrast agent to Gd-DTPA in DCE-MRI of the IFP of CK-160 cervical carcinoma xenografts. Clinical studies attempting to develop DCE-MRI-based assays of the IFP of cervical carcinomas should involve contrast agents with higher MW than Gd-DTPA.
背景
原发性肿瘤中的高间质液压力（IFP）与局部晚期宫颈癌患者无病生存时间较差相关。需要一种非侵入性的检测方法来识别 IFP 高度升高的宫颈癌患者，因为这些患者可能受益于特别激进的治疗。有人提出，使用钆二乙烯三胺五乙酸（Gd-DTPA）作为造影剂的动态对比增强磁共振成像（DCE-MRI）可能会提供有关宫颈癌 IFP 的有用信息。在这项临床前研究中，我们研究了使用分子量（MW）高于 Gd-DTPA 的造影剂的 DCE-MRI 是否优于基于 Gd-DTPA 的 DCE-MRI。
方法
对 CK-160 人宫颈癌异种移植瘤进行 DCE-MRI 检查，使用 Gd-DTPA（MW 为 0.55 kDa）或 gadomelitol（MW 为 6.5 kDa）作为造影剂，然后用 Millar SPC 320 导管侵入性测量肿瘤 IFP。DCE-MRI 采用 1.5-T 全身扫描仪和专为小鼠设计的开槽管谐振收发器线圈，以 0.23×0.23×2.0 mm³的空间分辨率和 14 s 的时间分辨率进行。通过使用 Tofts 各向同性转运模型和 Patlak 单向转运模型，从 DCE-MRI 记录中得出参数图像。
结果
当使用 gadomelitol 作为造影剂时，两种药代动力学模型的参数与肿瘤 IFP 之间存在显著的正相关关系。另一方面，当使用 Gd-DTPA 作为造影剂时，无法检测到 DCE-MRI 衍生参数与 IFP 之间的显著相关性。
结论
在 CK-160 宫颈癌异种移植瘤的 IFP DCE-MRI 中，gadomelitol 是 Gd-DTPA 的一种优越造影剂。试图开发基于 DCE-MRI 的宫颈癌 IFP 检测方法的临床研究应涉及分子量高于 Gd-DTPA 的造影剂。
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