Quantitative PET Imaging of VEGF Receptor Expression
Quantitative PET Imaging of VEGF Receptor Expression
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DOI：
10.1007/s11307-008-0172-1
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发表时间：
2009-01-01
影响因子：
3.1
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Chen, Kai;Cai, Weibo;Chen, Xiaoyuan
目的：血管内皮生长因子（VEGF）/VEGF受体（VEGFR）信号通路在肿瘤血管生成的调控中起着关键作用。VEGFR的定量正电子发射断层扫描（PET）成像将有助于规划是否以及何时开始抗血管生成治疗，并能够更稳健和有效地监测此类治疗。材料和方法：VEGF（121）与DOTA偶联（1，4，7，10-四氮杂十二烷N，N '，N“，N”"-四乙酸），然后用Cu-64标记，用于携带不同大小的人胶质母细胞瘤U87 MG肿瘤的小鼠的PET成像（n=15）。结果：Cu-64-DOTA-VEGF（121）的比活性为3.2GBq/mg。肿瘤中Cu-64-DOTA-VEGF（121）的摄取在肿瘤大小为约100-250 mm时达到峰值（3）。小肿瘤和大肿瘤都具有较低的示踪剂摄取，表明具有高VEGFR-2表达的肿瘤大小范围较窄。所有肿瘤均具有类似的低VEGFR-1表达。最重要的是，从PET成像获得的肿瘤摄取值与通过Western印迹测量的相对肿瘤组织VEGFR-2表达具有良好的线性相关性，其中基于注射后4小时的PET摄取，r（2）等于0.68。结论：小动物PET显像测量的肿瘤对Cu-64-DOTA-VEGF（121）的摄取反映了体内肿瘤VEGFR-2的表达水平。这种相关性可以促进癌症和潜在的其他血管生成相关疾病的未来治疗计划和治疗监测。
Purpose: Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) signaling pathway plays pivotal roles in regulating tumor angiogenesis. Quantitative positron emission tomography (PET) imaging of VEGFR will facilitate the planning of whether, and when, to start anti-angiogenic treatment and enable more robust and effective monitoring of such treatment.Materials and methods: VEGF(121) was conjugated with DOTA (1,4,7,10-tetra-azacylododecane N,N',N'',N'''-tetraacetic acid) and then labeled with Cu-64 for PET imaging of mice bearing different-sized human glioblastoma U87MG tumors (n=15). Western blotting and immunofluorescence staining of tumor tissue was carried out to correlate with/validate the imaging results.Results: The specific activity of Cu-64-DOTA-VEGF(121) was 3.2 GBq/mg. The uptake of Cu-64-DOTA-VEGF(121) in the tumor peaked when the tumor size was about 100-250 mm(3). Both small and large tumors had lower tracer uptake indicating a narrow range of tumor size with high VEGFR-2 expression. All tumors had similarly low VEGFR-1 expression. Most importantly, the tumor uptake value obtained from PET imaging had good linear correlation with the relative tumor tissue VEGFR-2 expression as measured by Western blot, where r(2) equals 0.68 based on the PET uptake at 4 h post-injection. Histology of the frozen tumor tissue corroborates well with the imaging results.Conclusion: The tumor uptake of Cu-64-DOTA-VEGF(121) measured by small-animal PET imaging reflects tumor VEGFR-2 expression level in vivo. Such correlation may facilitate future treatment planning and treatment monitoring of cancer and potentially other angiogenesis-related diseases.