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[容积灌注CT(VPCT)成像在兔VX2软组织肿瘤抗血管生成治疗中的可行性]

[Feasibility of volume perfusion CT (VPCT) imaging in antiangiogenic treatment of rabbit VX2 soft-tissue tumor].

作者信息

Yang Pei, Feng Xiao-wei, Ye Zhao-xiang, Li Xu-bin, Hou Yan, Liu Yi-tao, Xiao Jian-yu

机构信息

Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2013 May;35(5):341-6. doi: 10.3760/cma.j.issn.0253-3766.2013.05.005.

Abstract

OBJECTIVE

To explore the feasibility of volume perfusion CT imaging to dynamically monitor and evaluate the response of rabbit VX2 soft-tissue tumor to antiangiogenic treatment.

METHODS

To establish an experimental animal model of VX2 soft tissue tumor on 20 New Zealand white rabbits. Twenty rabbits were randomly divided into 2 groups. The therapy group was treated with recombinant human endostatin (3 mg·kg⁻¹·d⁻¹) for 7 days, and the control group received saline in the same dose only. Four times of CT volume perfusion scan were performed before treatment and on the second, forth, seventh days of treatment, respectively. The value of blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability (PMB) in the VX2 tumors were measured after scanning. The microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in the tumors were determined using immunohistochemical staining.

RESULTS

The tumor volume of the therapy group was (1.36 ± 0.73) cm³ on the forth day of treatment and (1.69 ± 0.68) cm³ on the seventh day of the treatment. The tumor volume of the control group was (2.35 ± 0.62) cm³ on the fourth day of treatment and (3.87 ± 0.93) cm³ on the seventh day of the treatment (P < 0.05). On the seventh day of treatment, tumor necrosis ratio of the therapy group and the control group was (25.58 ± 5.51)% and (42.93 ± 4.34)%, respectively (P < 0.05). Comparing the perfusion parameters between the two groups on the same day, and the second, forth, seventh days of treatment, the value of PMB of the therapy group was (70.36 ± 23.46) ml·100 ml⁻¹·min⁻¹, (79.64 ± 13.68) ml·100 ml⁻¹·min⁻¹ and (84.76 ± 3.55) ml·100 ml⁻¹·min⁻¹, respectively, and that in the control group was (26.61 ± 6.47) ml·100 ml⁻¹·min⁻¹, (33.74 ± 16.47) ml·100 ml⁻¹·min⁻¹ and (30.47 ± 10.64) ml·100 ml⁻¹·min⁻¹, respectively (P < 0.05). The value of BF in the therapy group and control group was (71.19 ± 12.21) ml·100 ml⁻¹·min⁻¹ and (43.56 ± 12.21) ml·100 ml⁻¹·min⁻¹, respectively, on the seventh day of treatment (P < 0.05). The parameters on different days in the same group were compared. In the control group, the value of BF on the seventh day of treatment was significantly lower than that before and on the second and forth days of treatment (P < 0.05). However, in the therapy group, the value of PMB on the second, forth, and seventh days of treatment was significantly higher than that before treatment (P < 0.05). MVD of tumor in the control group was increased gradually, whereas increased on the first day and then decreased more in the therapy group. The VEGF expressions did not differ significantly between the experimental and control groups.

CONCLUSIONS

Volume perfusion CT is helpful to quantify the tumor perfusion and evaluate the functional changes of tumor vasculature, and then evaluate the early therapeutic effect of antiangiogenic treatment.

摘要

目的

探讨容积灌注CT成像动态监测和评估兔VX2软组织肿瘤抗血管生成治疗反应的可行性。

方法

对20只新西兰白兔建立VX2软组织肿瘤实验动物模型。将20只兔子随机分为2组。治疗组用重组人内皮抑素(3 mg·kg⁻¹·d⁻¹)治疗7天,对照组仅给予相同剂量的生理盐水。在治疗前及治疗第2、4、7天分别进行4次CT容积灌注扫描。扫描后测量VX2肿瘤内的血流量(BF)、血容量(BV)、平均通过时间(MTT)和通透性(PMB)值。采用免疫组织化学染色法测定肿瘤内微血管密度(MVD)和血管内皮生长因子(VEGF)表达。

结果

治疗组在治疗第4天肿瘤体积为(1.36±0.73)cm³,治疗第7天为(1.69±0.68)cm³。对照组在治疗第4天肿瘤体积为(2.35±0.62)cm³,治疗第7天为(3.87±0.93)cm³(P<0.05)。治疗第7天,治疗组和对照组肿瘤坏死率分别为(25.58±5.51)%和(42.93±4.34)%(P<0.05)。比较两组在同一天以及治疗第2、4、7天的灌注参数,治疗组的PMB值分别为(70.36±23.46)ml·100 ml⁻¹·min⁻¹、(79.64±13.68)ml·100 ml⁻¹·min⁻¹和(84.76±3.55)ml·100 ml⁻¹·min⁻¹,对照组分别为(26.61±6.47)ml·100 ml⁻¹·min⁻¹、(33.74±16.47)ml·100 ml⁻¹·min⁻¹和(30.47±10.64)ml·100 ml⁻¹·min⁻¹(P<0.05)。治疗第7天,治疗组和对照组的BF值分别为(71.19±12.21)ml·100 ml⁻¹·min⁻¹和(43.56±12.21)ml·100 ml⁻¹·min⁻¹(P<0.05)。比较同一组不同时间的参数,对照组治疗第7天的BF值显著低于治疗前及治疗第2、4天(P<0.05)。然而,治疗组治疗第2、4、7天的PMB值显著高于治疗前(P<0.05)。对照组肿瘤的MVD逐渐增加,而治疗组在第1天增加,随后下降更多。实验组和对照组的VEGF表达差异无统计学意义。

结论

容积灌注CT有助于定量肿瘤灌注,评估肿瘤血管的功能变化,进而评估抗血管生成治疗的早期疗效。

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