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

ObjectivesTo determine whether the CKD-516 produces a significant change in vascular and metabolic parameters in PET/MRIMaterials and methodsWith 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.ResultsChanges 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 0.05).ConclusionsPET/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.研究目的：明确CKD-516是否可对正电子发射断层显像/磁共振成像（PET/MRI）检测中的血管及代谢参数产生显著改变。 材料与方法：本研究经机构动物实验伦理审查委员会批准，对9只家兔双侧背部肌肉植入的18枚VX2肿瘤瘤株开展评估。分别于给药前、给药后4小时及给药后1周，对给予0.7 mg/kg剂量血管破坏剂CKD-516的给药组（n=10）及给予生理盐水的对照组（n=8）家兔进行连续PET/MRI扫描。采用线性混合模型对两组的PET/MRI衍生参数及其区间变化进行组间比较；同时采用该模型对各组内的各项参数进行组内比较。 结果：给药组在给药后4小时随访时的体积转运常数（Ktrans）及钆剂浓度-时间曲线60秒内初始面积（iAUC）的变化量均显著大于对照组（均值分别为-39.91% vs. -6.04%，P=0.018；-49.71% vs. +6.23%，P=0.013）。给药组在给药后1周随访时的代谢肿瘤体积（MTV）变化量显著小于对照组（均值分别为+118.34% vs. +208.87%，P=0.044）。对给药组的连续检测结果显示，Ktrans与iAUC在4小时随访时点均有所下降（P 0.05）。 结论：PET/MRI可同时监测不同时间点的血管及代谢参数变化，并证实血管破坏剂CKD-516诱导的血管变化早于代谢变化。