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钆喷酸葡胺与超小型超顺磁性氧化铁用于小鼠人结肠癌肿瘤血管生成的动态对比增强磁共振成像

Gadopentetate dimeglumine versus ultrasmall superparamagnetic iron oxide for dynamic contrast-enhanced MR imaging of tumor angiogenesis in human colon carcinoma in mice.

作者信息

de Lussanet Quido G, Backes Walter H, Griffioen Arjan W, van Engelshoven Jos M A, Beets-Tan Regina G H

机构信息

Department of Radiology, Maastricht University Hospital, P. Debyelaan 25, PO Box 5800, 6202 AZ Maastricht, the Netherlands.

出版信息

Radiology. 2003 Nov;229(2):429-38. doi: 10.1148/radiol.2292021007.

DOI:10.1148/radiol.2292021007
PMID:14595147
Abstract

PURPOSE

To compare the kinetic physiologic properties of a clinical contrast agent, gadopentetate dimeglumine, with those of ultrasmall superparamagnetic iron oxide (USPIO) particles for dynamic contrast material-enhanced magnetic resonance (MR) imaging of tumor angiogenesis in human colon carcinoma in mice with a clinical MR imaging unit.

MATERIALS AND METHODS

Thirty-two mice with human colon carcinoma were injected with either gadopentetate dimeglumine (n = 16) or USPIO (n = 16) for dynamic contrast-enhanced MR imaging and pre- and postcontrast T2 and T2* measurements. Dynamic contrast-enhanced MR imaging measurements were analyzed by using a two-compartment model to calculate the endothelial transfer coefficient surface area product (KPS) for the tumor microvasculature, the reflux coefficient (k), and the fractional plasma volume (fPV). KPS, k, and fPV maps were compared with histologic microvessel density (MVD) and used to observe differences between core and rim regions of tumor.

RESULTS

Results in 30 mice (15 in the gadopentetate dimeglumine group and 15 in the USPIO group) could be used. KPS values measured with both agents correlated well with MVD in hot spots (gadopentetate dimeglumine: r = 0.6, P =.02; USPIO: r = 0.6, P =.01). No significant difference (P =.4) in correlation was found between the two agents. Both USPIO and gadopentetate dimeglumine demonstrated higher MVD and KPS values in tumor rim than in tumor core (P <.01). Tumor k values correlated poorly with whole-tumor MVD for both gadopentetate dimeglumine (r = 0.3, P =.4) and USPIO (r = 0.2, P =.6), while fPV values correlated well with whole-tumor MVD for USPIO (r = 0.6, P =.02) but not gadopentetate dimeglumine (r = -0.01, P =.98). T2 and T2* measurements showed small differences between areas of high and low angiogenic activity with both agents.

CONCLUSION

The kinetic physiologic properties of gadopentetate dimeglumine are as good as those of USPIO for dynamic contrast-enhanced MR imaging for calculating KPS as a measurement of angiogenesis in human colon carcinoma. Further studies with patients may reveal whether gadopentetate dimeglumine might be used for this purpose in clinical practice.

摘要

目的

使用临床磁共振成像设备,比较临床造影剂钆喷酸葡胺与超小超顺磁性氧化铁(USPIO)颗粒在小鼠人结肠癌肿瘤血管生成动态对比剂增强磁共振(MR)成像中的动力学生理特性。

材料与方法

32只患有人类结肠癌的小鼠,分别注射钆喷酸葡胺(n = 16)或USPIO(n = 16)用于动态对比增强MR成像以及对比剂注射前后的T2和T2*测量。通过使用双室模型分析动态对比增强MR成像测量结果,以计算肿瘤微血管系统的内皮转运系数表面积乘积(KPS)、回流系数(k)和血浆容积分数(fPV)。将KPS、k和fPV图与组织学微血管密度(MVD)进行比较,并用于观察肿瘤核心区和边缘区之间的差异。

结果

30只小鼠(钆喷酸葡胺组15只,USPIO组15只)的结果可用。两种造影剂测得的KPS值在热点区域与MVD均具有良好的相关性(钆喷酸葡胺:r = 0.6,P =.02;USPIO:r = 0.6,P =.01)。两种造影剂之间在相关性方面未发现显著差异(P =.4)。USPIO和钆喷酸葡胺在肿瘤边缘的MVD和KPS值均高于肿瘤核心(P <.01)。钆喷酸葡胺(r = 0.3,P =.4)和USPIO(r = 0.2,P =.6)的肿瘤k值与全肿瘤MVD的相关性均较差,而USPIO的fPV值与全肿瘤MVD具有良好的相关性(r = 0.6,P =.02),钆喷酸葡胺则不然(r = -0.01,P =.98)。T2和T2*测量显示,两种造影剂在高血管生成活性区和低血管生成活性区之间的差异较小。

结论

在用于动态对比增强MR成像以计算KPS作为人结肠癌血管生成测量指标方面,钆喷酸葡胺的动力学生理特性与USPIO一样好。对患者的进一步研究可能会揭示钆喷酸葡胺在临床实践中是否可用于此目的。

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