GE Healthcare MDx Research, The Grove Centre, Amersham, UK.
J Nucl Med. 2011 Mar;52(3):424-30. doi: 10.2967/jnumed.110.077479. Epub 2011 Feb 14.
Arginine-glycine-aspartate (RGD)-binding α(V)β(3)-integrin and α(V)β(5)-integrin play key roles in tumor angiogenesis. We examined an (18)F-labeled small peptide (fluciclatide [United States Adopted Name (ASAN)-approved, International Nonproprietary Name (INN)-proposed name], previously referred to as AH111585) containing an RGD sequence. Fluciclatide binds with a high (nM) affinity to α(V)β(3)-integrin and α(V)β(5)-integrin, which are highly expressed on tumors and the tumor neovasculature. In this study, (18)F-fluciclatide was used to examine the response of human glioblastoma xenografts to treatment with the antiangiogenic agent sunitinib.
U87-MG tumor uptake of (18)F-fluciclatide was determined by small-animal PET after longitudinal administration of the antiangiogenic agent sunitinib (a 2-wk dosing regimen). Tumor sizes were measured throughout the study, and tumor volumes were calculated. Tumor microvessel density (MVD) after therapy was also analyzed.
Dynamic small-animal PET of (18)F-fluciclatide uptake after administration of the clinically relevant antiangiogenic agent sunitinib revealed a reduction in the tumor uptake of (18)F-fluciclatide compared with that in vehicle-treated controls over the 2-wk dosing regimen. Skeletal muscle, used as a reference tissue, showed equivalent (18)F-fluciclatide uptake in both therapy and control groups. A reduction in tumor MVD was also observed after treatment with the antiangiogenic agent. No significant changes in tumor volume were observed in the 2 groups.
The data demonstrated that (18)F-fluciclatide detected changes in tumor uptake after acute antiangiogenic therapy markedly earlier than any significant volumetric changes were observable. These results suggest that this imaging agent may provide clinically important information for guiding patient care and monitoring the response to antiangiogenic therapy.
精氨酸-甘氨酸-天冬氨酸（RGD）结合α（V）β（3）-整联蛋白和α（V）β（5）-整联蛋白在肿瘤血管生成中起关键作用。我们研究了一种（18）F 标记的小肽（fluciclatide [美国采用的名称（ASAN）批准，国际非专利名称（INN）提议的名称]，以前称为 AH111585），其包含 RGD 序列。Fluciclatide 以高（nM）亲和力与肿瘤和肿瘤新生血管中高度表达的α（V）β（3）-整联蛋白和α（V）β（5）-整联蛋白结合。在这项研究中，（18）F-fluciclatide 用于检查抗血管生成剂 sunitinib 对人胶质母细胞瘤异种移植物的反应。
通过长期给予抗血管生成剂 sunitinib（2 周给药方案）后，小动物 PET 测定 U87-MG 肿瘤对（18）F-fluciclatide 的摄取。在整个研究过程中测量肿瘤大小，并计算肿瘤体积。还分析了治疗后的肿瘤微血管密度（MVD）。
在给予临床相关的抗血管生成剂 sunitinib 后，（18）F-fluciclatide 摄取的动态小动物 PET 显示，与载体处理对照相比，在 2 周的给药方案中，肿瘤对（18）F-fluciclatide 的摄取减少。用作参考组织的骨骼肌在治疗组和对照组中均显示出相等的（18）F-fluciclatide 摄取。在用抗血管生成剂治疗后，肿瘤 MVD 也减少。两组肿瘤体积均无明显变化。
数据表明，（18）F-fluciclatide 在急性抗血管生成治疗后检测到肿瘤摄取的变化，比任何明显的体积变化都要早得多。这些结果表明，这种成像剂可能为指导患者护理和监测抗血管生成治疗反应提供重要的临床信息。
Zotero 插件