Quantitative Evaluation of Tumor Early Response to a Vascular-Disrupting Agent with Dynamic PET.
Quantitative Evaluation of Tumor Early Response to a Vascular-Disrupting Agent with Dynamic PET.
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DOI：
10.1007/s11307-015-0854-4
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发表时间：
2015-12
影响因子：
3.1
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Guo N;Zhang F;Zhang X;Guo J;Lang L;Kiesewetter DO;Niu G;Li Q;Chen X
本研究的目的是使用动态 [18F]FPPRGD2 正电子发射断层扫描 (PET) 和动力学参数估计来评估肿瘤对血管干扰剂 (VDA) VEGF121/重组毒素 gelonin (rGel) 的早期反应。选择两种肿瘤异种移植模型：U87MG（高度血管化）和A549（中度血管化），并将两者随机分为治疗组和对照组。自 VEGF121/rGel 治疗开始后的第 0 天（基线）、第 1 和第 3 天，使用靶向整合素 αvβ3 的 [18F]FPPRGD2 进行 60 分钟动态 PET 扫描。将动态 PET 衍生结合电位 (BPND) 和参数图与示踪剂施用后 1 小时的肿瘤摄取 (%ID/g) 和静态 PET 图像进行比较。 VEGF121/rGel治疗后U87MG肿瘤的生长明显延迟。 A549 肿瘤对相同的治疗没有反应。与对照组相比，治疗后的 U87MG 肿瘤的 BPND 在第 1 天显着下降（p<0.05），并且在第 3 天差异更加显着（p<0.01）。然而，直到第 3 天，从 1 小时时间点的静态图像得出的示踪剂摄取 (%ID/g) 并未显示出治疗肿瘤和对照肿瘤之间的显着差异。在治疗肿瘤和对照 A549 肿瘤之间发现示踪剂摄取 (%ID/g) 或 BPND 几乎没有差异。考虑到示踪剂在肿瘤中的保留以及治疗后由于肿瘤脉管系统受损而导致的清除速度较慢，代表实际特异性结合部分的BPND似乎比从静态图像导出的半定量参数（例如%ID/g）更灵敏和准确，以评估肿瘤对VDA治疗的早期反应。基于动态PET和[18F]FPPRGD2的定量分析显示出在早期VEGF121/rGel治疗过程中区分有效和无效治疗的优势，因此在评估治疗反应方面比静态PET更敏感。
The purpose of this study is to evaluate the early response of tumors to a vascular-disrupting agent (VDA) VEGF121/recombinant toxin gelonin (rGel) using dynamic [18F]FPPRGD2 positron emission tomography (PET) and kinetic parameter estimation. Two tumor xenograft models: U87MG (highly vascularized) and A549 (moderately vascularized), were selected, and both were randomized into treatment and control groups. Sixty-minute dynamic PET scans with [18F]FPPRGD2 that targets to integrin αvβ3 were performed at days 0 (baseline), 1, and 3 since VEGF121/rGel treatment started. Dynamic PET-derived binding potential (BPND) and parametric maps were compared with tumor uptake (%ID/g) and the static PET image at 1 h after the tracer administration. The growth of U87MG tumor was obviously delayed upon VEGF121/rGel treatment. A549 tumor was not responsive to the same treatment. BPND of treated U87MG tumors decreased significantly at day 1 (p<0.05), and the difference was more significant at day 3 (p<0.01), compared with the control group. However, the tracer uptake (%ID/g) derived from static images at 1-h time point did not show significant difference between the treated and control tumors until day 3. Little difference in tracer uptake (%ID/g) or BPND was found between treated and control A549 tumors. Considering the tracer retention in tumor and the slower clearance due to damaged tumor vasculature after treatment, BPND representing the actual specific binding portion appears to be more sensitive and accurate than the semiquantitative parameters (such as %ID/g) derived from static images to assess the early response of tumor to VDA treatment. Quantitative analysis based on dynamic PET with [18F]FPPRGD2 shows advantages in distinguishing effective from ineffective treatment during the course of VEGF121/rGel therapy at early stage and is therefore more sensitive in assessing therapy response than static PET.
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影响因子：
8.4
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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