First-in-human DR5 PET reveals insufficient DR5 expression in patients with gastrointestinal cancer
Background Death receptor 5 (DR5) is a promising therapeutic target for cancer therapy. However, many clinical trials of DR5 agonists failed to show significant therapeutic efficacy in patients with cancer. The study aimed to investigate the feasibility of using 89Zr-CTB006 positron emission tomogra...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2021-07-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/9/7/e002926.full |
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| _version_ | 1846173064874688512 |
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| author | Feng Wang Yan Zhang Hua Zhu Jin Ding Nan Li Tong Zhou Jun Zhao Zhi Yang Yingjie Li Xinyu Wang Yunfeng Yao Shujing Wang Lixin Ding Aiwen Wu |
| author_facet | Feng Wang Yan Zhang Hua Zhu Jin Ding Nan Li Tong Zhou Jun Zhao Zhi Yang Yingjie Li Xinyu Wang Yunfeng Yao Shujing Wang Lixin Ding Aiwen Wu |
| author_sort | Feng Wang |
| collection | DOAJ |
| description | Background Death receptor 5 (DR5) is a promising therapeutic target for cancer therapy. However, many clinical trials of DR5 agonists failed to show significant therapeutic efficacy in patients with cancer. The study aimed to investigate the feasibility of using 89Zr-CTB006 positron emission tomography (PET) for noninvasive imaging of DR5 expression in preclinical models and patients with gastrointestinal (GI) cancers.Methods Balb/c, Sp2/0 xenograft and patient-derived tumor xenograft were employed for micro-PET/CT imaging in vivo. In the clinical study, patients with GI cancers planning to undergo surgical operation were enrolled and underwent 18F-FDG and 89Zr-CTB006 PET/CT. The tumor tissues were obtained through surgical operation and DR5 expression levels were confirmed by RNAscope.Results Preclinical studies showed that 89Zr-CTB006 PET could specifically detect DR5 expression levels in vivo. Twenty-one patients, including nine gastric cancers and 12 colorectal cancers, were enrolled. The biodistribution showed high uptake in the liver and spleen and low uptake in the brain, lung and muscle with an acceptable whole-body dosimetry of 0.349 mSv/MBq. Strikingly, the adrenal glands maintained stable high uptake over the entire examination in all patients. The tumor lesions showed different levels of uptake of 89Zr-CTB006 with a mean maximum standardized uptake value (SUVmax) of 6.63±3.29 (range 1.8–13.8). Tumor tissue was obtained from 18 patients, and 89Zr-CTB006 uptake in patients with RNAscope scores of 3–4 was significantly higher than that in patients with scores of 0–2. An SUVmax of 9.3 at 48 hours and 6.3 at 72 hours could be used to discriminate the DR5 expression status of tumors both with a sensitivity and specificity of 100% and 92.9%, respectively.Conclusions 89Zr-CTB006 PET/CT is capable of detecting DR5 expression in cancer patients and is a promising approach to screen patients with DR5 overexpression. |
| format | Article |
| id | doaj-art-e2b4c8d433ab485f9742e9d48c36a403 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2021-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-e2b4c8d433ab485f9742e9d48c36a4032024-11-08T15:20:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-07-019710.1136/jitc-2021-002926First-in-human DR5 PET reveals insufficient DR5 expression in patients with gastrointestinal cancerFeng Wang0Yan Zhang1Hua Zhu2Jin Ding3Nan Li4Tong Zhou5Jun Zhao6Zhi Yang7Yingjie Li8Xinyu Wang9Yunfeng Yao10Shujing Wang11Lixin Ding12Aiwen Wu13Department of Neurology, Seventh People`s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDrug Clinical Trial Institution, Shanghai Mental Health Center, Shanghai, ChinaDepartment of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, ChinaDepartment of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, ChinaNMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Beijing, China1Department of Cancer Epidemiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China5 China Rehabilitation Research Center, Beijing, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaDepartment of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, ChinaDepartment of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaBackground Death receptor 5 (DR5) is a promising therapeutic target for cancer therapy. However, many clinical trials of DR5 agonists failed to show significant therapeutic efficacy in patients with cancer. The study aimed to investigate the feasibility of using 89Zr-CTB006 positron emission tomography (PET) for noninvasive imaging of DR5 expression in preclinical models and patients with gastrointestinal (GI) cancers.Methods Balb/c, Sp2/0 xenograft and patient-derived tumor xenograft were employed for micro-PET/CT imaging in vivo. In the clinical study, patients with GI cancers planning to undergo surgical operation were enrolled and underwent 18F-FDG and 89Zr-CTB006 PET/CT. The tumor tissues were obtained through surgical operation and DR5 expression levels were confirmed by RNAscope.Results Preclinical studies showed that 89Zr-CTB006 PET could specifically detect DR5 expression levels in vivo. Twenty-one patients, including nine gastric cancers and 12 colorectal cancers, were enrolled. The biodistribution showed high uptake in the liver and spleen and low uptake in the brain, lung and muscle with an acceptable whole-body dosimetry of 0.349 mSv/MBq. Strikingly, the adrenal glands maintained stable high uptake over the entire examination in all patients. The tumor lesions showed different levels of uptake of 89Zr-CTB006 with a mean maximum standardized uptake value (SUVmax) of 6.63±3.29 (range 1.8–13.8). Tumor tissue was obtained from 18 patients, and 89Zr-CTB006 uptake in patients with RNAscope scores of 3–4 was significantly higher than that in patients with scores of 0–2. An SUVmax of 9.3 at 48 hours and 6.3 at 72 hours could be used to discriminate the DR5 expression status of tumors both with a sensitivity and specificity of 100% and 92.9%, respectively.Conclusions 89Zr-CTB006 PET/CT is capable of detecting DR5 expression in cancer patients and is a promising approach to screen patients with DR5 overexpression.https://jitc.bmj.com/content/9/7/e002926.full |
| spellingShingle | Feng Wang Yan Zhang Hua Zhu Jin Ding Nan Li Tong Zhou Jun Zhao Zhi Yang Yingjie Li Xinyu Wang Yunfeng Yao Shujing Wang Lixin Ding Aiwen Wu First-in-human DR5 PET reveals insufficient DR5 expression in patients with gastrointestinal cancer Journal for ImmunoTherapy of Cancer |
| title | First-in-human DR5 PET reveals insufficient DR5 expression in patients with gastrointestinal cancer |
| title_full | First-in-human DR5 PET reveals insufficient DR5 expression in patients with gastrointestinal cancer |
| title_fullStr | First-in-human DR5 PET reveals insufficient DR5 expression in patients with gastrointestinal cancer |
| title_full_unstemmed | First-in-human DR5 PET reveals insufficient DR5 expression in patients with gastrointestinal cancer |
| title_short | First-in-human DR5 PET reveals insufficient DR5 expression in patients with gastrointestinal cancer |
| title_sort | first in human dr5 pet reveals insufficient dr5 expression in patients with gastrointestinal cancer |
| url | https://jitc.bmj.com/content/9/7/e002926.full |
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