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使用PET/MRI在兔VX2肌内肿瘤模型中监测肿瘤对血管破坏剂CKD-516的反应:血管和代谢参数的同步评估

Monitoring tumor response to the vascular disrupting agent CKD-516 in a rabbit VX2 intramuscular tumor model using PET/MRI: Simultaneous evaluation of vascular and metabolic parameters.

作者信息

Ahn Su Yeon, Goo Jin Mo, Lee Kyung Hee, Ha Seunggyun, Paeng Jin Chul

机构信息

Department of Radiology, Seoul National University College of Medicine, and Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea.

Cancer Research Institute, Seoul National University, Seoul, Korea.

出版信息

PLoS One. 2018 Feb 13;13(2):e0192706. doi: 10.1371/journal.pone.0192706. eCollection 2018.

DOI:10.1371/journal.pone.0192706
PMID:29438381
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5811032/
Abstract

OBJECTIVES

To determine whether the CKD-516 produces a significant change in vascular and metabolic parameters in PET/MRI.

MATERIALS AND METHODS

With institutional Animal Care and Use Committee approval, 18 VX2 carcinoma tumors implanted in bilateral back muscles of 9 rabbits were evaluated. Serial PET/MRI were performed before, 4 hours after and 1-week after vascular disrupting agent, CKD-516 at a dose of 0.7 mg/kg (treated group, n = 10) or saline (control group, n = 8) administration. PET/MRI-derived parameters and their interval changes were compared between the treated and control group by using the linear mixed model. Each parameter within each group was also compared by using the linear mixed model.

RESULTS

Changes of the volume transfer coefficient (Ktrans) and the initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) in the treated group were significantly larger compared with those in the control group at 4-hour follow-up (mean, -39.91% vs. -6.04%, P = 0.018; and -49.71% vs. +6.23%, P = 0.013). Change of metabolic tumor volume (MTV) in the treated group was significantly smaller compared with that in the control group at 1-week follow-up (mean, +118.34% vs. +208.87%, P = 0.044). Serial measurements in the treated group revealed that Ktrans and iAUC decreased at 4-hour follow-up (P < 0.001) and partially recovered at 1-week follow-up (P = 0.001 and 0.024, respectively). MTV increased at a 4-hour follow-up (P = 0.038) and further increased at a 1-week follow-up (P < 0.001), while total lesion glycolysis (TLG) did not show a significant difference between the time points. SUVmax and SUVmean did not show significant interval changes between time points (P > 0.05).

CONCLUSIONS

PET/MRI is able to monitor the changes of vascular and metabolic parameters at different time points simultaneously, and confirmed that vascular changes precede the metabolic changes by VDA, CKD-516.

摘要

目的

确定CKD - 516是否会使PET/MRI中的血管和代谢参数产生显著变化。

材料与方法

经机构动物护理和使用委员会批准,对9只兔双侧背部肌肉中植入的18个VX2癌肿瘤进行评估。在给予剂量为0.7 mg/kg的血管破坏剂CKD - 516(治疗组,n = 10)或生理盐水(对照组,n = 8)之前、之后4小时和1周后进行系列PET/MRI检查。使用线性混合模型比较治疗组和对照组之间PET/MRI衍生参数及其间隔变化。每组内的每个参数也使用线性混合模型进行比较。

结果

在4小时随访时,治疗组的容积转运系数(Ktrans)和钆浓度 - 时间曲线下60秒内的初始面积(iAUC)变化与对照组相比显著更大(平均值分别为 - 39.91%对 - 6.04%,P = 0.018;以及 - 49.71%对 + 6.23%,P = 0.013)。在1周随访时,治疗组的代谢肿瘤体积(MTV)变化与对照组相比显著更小(平均值分别为 + 118.34%对 + 208.87%,P = 0.044)。治疗组的系列测量显示Ktrans和iAUC在4小时随访时下降(P < 0.001),并在1周随访时部分恢复(分别为P = 0.001和0.024)。MTV在4小时随访时增加(P = 0.038),并在1周随访时进一步增加(P < 0.001),而总病变糖酵解(TLG)在各时间点之间未显示出显著差异。SUVmax和SUVmean在各时间点之间未显示出显著的间隔变化(P > 0.05)。

结论

PET/MRI能够同时监测不同时间点的血管和代谢参数变化,并证实血管破坏剂CKD - 516导致的血管变化先于代谢变化。

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Radiology. 2016 Jan;278(1):104-13. doi: 10.1148/radiol.2015141974. Epub 2015 Jul 22.
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