文章基本信息

标题：CAIX-targeting radiotracers for hypoxia imaging in head and neck cancer models
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作者：Fokko J. Huizing ; Javad Garousi ; Jasper Lok 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2019
卷号：9
期号：1
页码：1-10
DOI：10.1038/s41598-019-54824-5
出版社：Springer Nature
摘要：Hypoxia-induced carbonic anhydrase IX (CAIX) expression is a prognostic marker in solid tumors. In recent years many radiotracers have been developed, but a fair comparison of these compounds is not possible because of the diversity in tumor models and other experimental parameters. In this study we performed a direct in vivo comparison of three promising CAIX targeting radiotracers in xenografted head and neck cancer models. The biodistribution of [ 111 In]In-DOTA-ZCAIX:2 was directly compared with [ 111 In]In-DTPA-G250-F(ab') 2 and [ 111 In] In-DTPA-G250 in female BALB/C nu/nu mice bearing two HNSCC xenografts with different levels of CAIX expression. In vivo biodistribution was quantified by means of microSPECT/CT scans and ex vivo biodistribution was determined with the use of a γ-counter. Tumors were snap frozen and sections were stained for CAIX expression, vessels, hypoxia (pimonidazole) and tumor blood perfusion. Tracer uptake was significantly higher in SSCNij153 tumors compared to SCCNij185 tumors for [ 111 In]In-DOTA-HE3-ZCAIX:2: 0.32 ± 0.03 versus 0.18 ± 0.01%ID/g,(p = 0.003) 4 h p.i., for [ 111 In]In-DTPA-girentuximab-F(ab') 2 : 3.0 ± 0.5%ID/g and 1.2 ± 0.1%ID/g (p = 0.03), 24 h p.i. and for [ 111 In]In-DTPA-girentuximab: 30 ± 2.1%ID/g and 7.0 ± 1.0%ID/g (p = 0.0002) 72 h p.i. SPECT imaging with both [ 111 In]In-DTPA-girentuximab-F(ab') 2 and [ 111 In]In-DTPA-girentuximab showed a clear difference in tracer distribution between the two tumor models. The whole IgG, i.e. [ 111 In]In-DTPA-girentuximab, showed the highest tumor-to-muscle ratio. We showed that different CAIX-targeting radiotracers can discriminate a low CAIX-expressing tumor from a high CAIX-expressing head and neck cancer xenografts model. In these hypoxic head and neck xenograft models [ 111 In]In-DTPA-girentuximab showed the most promising results.