Stratification of 18F-Labeled PET Imaging Agents for the Assessment of Antiangiogenic Therapy Responses in Tumors
Stratification of 18F-Labeled PET Imaging Agents for the Assessment of Antiangiogenic Therapy Responses in Tumors
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DOI：
10.2967/jnumed.112.115824
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发表时间：
2013-09-01
影响因子：
9.3
通讯作者：
Bhakoo, Kishore K.
中科院分区：
文献类型：
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作者：
Goggi, Julian L.;Bejot, Romain;Bhakoo, Kishore K.
成功的抗血管生成疗法已被开发用于治疗各种癌症，但并非所有患者都有反应。因此，早期确定治疗效果对于患者管理至关重要。本研究旨在评估各种PET成像生物标志物在早期确定抗血管生成剂阿西替尼（一种多受体酪氨酸激酶抑制剂）治疗具有不同生物学特征的肿瘤的反应中的效用。研究方法：携带U87-MG和MDA-MB-231皮下肿瘤的小鼠用阿西替尼（25 mg/kg，每天腹膜内，持续10天）处理，并且用卡尺测量评估肿瘤体积。同时用F-18-FDG、3 '-脱氧-3'-F-18-氟胸苷（F-18-FLT）和2-F-18-氟乙基-三唑基缀合的c（RGDyK）肽（F-18-FtRGD）对动物进行纵向成像，以确定用于测量2种肿瘤类型早期治疗反应的最佳放射性药物。结果如下：每天给予阿西替尼成功地延缓了U87-MG和MDA-MB-231皮下肿瘤的生长，从治疗后第7天开始观察到肿瘤体积的显著差异。F-18-FDG仅在治疗后第10天在U87-MG荷瘤动物和MDA-MB-231荷瘤动物中显示治疗功效反应。F-18-FLT提供了治疗反应的早期检测，揭示了在第3天携带U87-MG肿瘤的动物和在第7天携带生长更缓慢的MDA-MB-231肿瘤的动物中药物和溶剂处理的动物之间的显著差异。F-18-FtRGD显示肿瘤保留的快速变化，在U87-MG荷瘤动物中，到第7天达到显著性;相反，在MDA-MB-231荷瘤动物中未观察到肿瘤保留的显著差异。结论：不同肿瘤类型的放射性药物纵向显像表现出不同的特征，这取决于肿瘤的生物学特性。这些研究可以提供临床上重要的信息，以指导患者的管理和监测反应的抗血管生成治疗与最佳的非侵入性成像剂在相关的癌症类型。
Successful antiangiogenic therapies have been developed for the treatment of various cancers, but not all patients respond. Therefore, the early determination of therapy efficacy is essential for patient management. This study was done to evaluate the utility of various PET imaging biomarkers for early determination of the response to therapy with the antiangiogenic agent axitinib, a multiple receptor tyrosine kinase inhibitor, in tumors with diverse biologic characteristics. Methods: Mice bearing U87-MG and MDA-MB-231 subcutaneous tumors were treated with axitinib (25 mg/kg intraperitoneally daily for 10 d), and tumor volumes were assessed with caliper measurements. The animals were concurrently imaged longitudinally with F-18-FDG, 3'-deoxy-3'-F-18-fluorothymidine (F-18-FLT), and 2-F-18-fluoroethyl-triazolyl conjugated c(RGDyK) peptide (F-18-FtRGD) to determine the optimal radiopharmaceutical for measuring the early treatment response in the 2 tumor types. Results: Daily administration of axitinib successfully retarded the growth of both U87-MG and MDA-MB-231 subcutaneous tumors, with significant differences in tumor volumes being observed from day 7 after therapy on. F-18-FDG revealed a treatment efficacy response only at day 10 after treatment in both U87-MG tumor-bearing and MDA-MB-231 tumor-bearing animals. F-18-FLT afforded earlier detection of the therapy response, revealing a significant difference between drug-and vehicle-treated animals at day 3 for animals bearing U87-MG tumors and at day 7 for animals bearing the more slowly growing MDA-MB-231 tumors. F-18-FtRGD showed a rapid change in tumor retention that reached significance by day 7 in U87-MG tumor-bearing animals; in contrast, no significant difference in tumor retention was observed in MDA-MB-231 tumor-bearing animals. Conclusion: Longitudinal imaging with different radiopharmaceuticals displays various characteristics in different tumor types, depending on their biologic characteristics. Such studies may provide clinically important information to guide patient management and monitor the response to antiangiogenic therapy with the optimum noninvasive imaging agent in the relevant cancer type.