Quantification of Tumor Vascular Permeability and Blood Volume by Positron Emission Tomography.
Quantification of Tumor Vascular Permeability and Blood Volume by Positron Emission Tomography.
复制标题
通过正电子发射断层扫描对肿瘤血管渗透性和血量进行量化。
作者：
Chen H;Tong X;Lang L;Jacobson O;Yung BC;Yang X;Bai R;Kiesewetter DO;Ma Y;Wu H;Niu G;Chen X
目的：伊文思蓝（EB）是一种偶氮染料，可与血清白蛋白定量结合。利用白蛋白结合、NOTA缀合的截短伊文思蓝（NEB）染料衍生的PET示踪剂，我们旨在建立一种通过非侵入性PET评估恶性肿瘤血管通透性的策略。实验设计：在包括INS-1大鼠胰岛素瘤、UM-SCC-22 B人头颈癌和U-87 MG人胶质母细胞瘤的三种异种移植肿瘤模型中使用[18 F]FAl-NEB进行60分钟动态PET。通过肿瘤和血液时间-活性曲线（TAC，表示为Ps）之间的斜率的差异来量化肿瘤血管渗透性。该方法进一步证实了EB提取和比色测定，并与动态对比增强磁共振成像（DCE-MRI）计算的相关性。在用贝伐单抗或多柔比星治疗后的U-87 MG和UM-SCC-22 B肿瘤模型中，用NEB PET评估不同时间点的肿瘤脉管系统的变化。结果：由多个时间点静态图像的肿瘤和血液TAC计算的Ps值与动态图像的Ps值一致。此外，Ps与提取的EB浓度和从DCE-MRI产生的KPS-MRI显示出正的和显著的相关性，这进一步证实了该方法的合理性。早在治疗后8小时，NEB PET就可以在U-87 MG肿瘤中显示贝伐珠单抗的抗血管生成作用，表现为Ps显著降低。与对照组相比，贝伐单抗处理的UM-SCC-22 B肿瘤中Ps没有显著变化。然而，阿霉素治疗的UM-SCC-22 B肿瘤中Ps的显著变化被高估。结论：我们成功地开发了一种相对方便和新颖的策略，使用NEB PET评估血管通透性和血容量。该方法在评价血管通透性、促进药物递送和监测肿瘤对影响肿瘤血管生成的治疗剂的反应方面将是有利的。
Purpose: Evans Blue (EB) is an azo dye that binds quantitatively with serum albumin. With an albumin binding, NOTA conjugated truncated Evan's blue (NEB) dye derived PET tracer, we aimed to establish a strategy for evaluating vascular permeability in malignant tumors via non-invasive PET. Experimental design: Sixty-minute dynamic PET using [18F]FAl-NEB was performed in three xenograft tumor models including INS-1 rat insulinoma, UM-SCC-22B human head and neck carcinoma and U-87 MG human glioblastoma. Tumor vascular permeability was quantified by the difference of the slopes between tumor and blood time-activity curve (TACs, expressed as Ps). The method was further substantiated by EB extraction and colorimetric assay and correlates with that calculated from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). The changes in tumor vasculature at different time points were assessed with NEB PET in U-87 MG and UM-SCC-22B tumor models after treatment with bevacizumab or doxorubicin. Result: The Ps values calculated from tumor and blood TACs from multiple time-point static images are consistent with those from dynamic images. Moreover, the Ps showed a positive and significant correlation with extracted EB concentration and KPS-MRI generated from DCE-MRI, which further confirmed the soundness of this methodology. The antiangiogenic effect of bevacizumab could be revealed by NEB PET in U-87 MG tumors as early as 8 hrs after therapy, demonstrated by a substantial decrease of Ps. On the contrary, there was no significant change of Ps in bevacizumab treated UM-SCC-22B tumors, compared with control group. However, the significant changes of Pswere overestimated in doxorubicin treated UM-SCC-22B tumors. Conclusions: We successfully developed a relatively convenient and novel strategy to evaluate vascular permeability and blood volume using NEB PET. This method will be advantageous in evaluating vascular permeability, promoting drug delivery, and monitoring tumor response to therapeutics that affect tumor angiogenesis.
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影响因子：
5.4
作者：
Barnes SL;Whisenant JG;Loveless ME;Yankeelov TE
通讯作者：
Yankeelov TE
影响因子：
4.8
作者：
Ferrier, Moira C.;Sarin, Hemant;Butman, John A.
通讯作者：
Butman, John A.
影响因子：
3.1
作者：
Chen, Haojun;Li, Yimin;An, Hanxiang
通讯作者：
An, Hanxiang
影响因子：
3.3
作者：
Cyran, Clemens C.;Sennino, Barbara;Fu, Yanjun;Rogut, Victor;Shames, David M.;Chaopathomkul, Bundit;Wendland, Michael F.;McDonald, Donald M.;Brasch, Robert C.;Raatschen, Hans-Juergen
通讯作者：
Raatschen, Hans-Juergen
影响因子：
15.9
作者：
Gibson, JG II;Evans, WA Jr
通讯作者：
Evans, WA Jr