PMID- 34301815 OWN - NLM STAT- MEDLINE DCOM- 20220111 LR - 20220119 IS - 2051-1426 (Electronic) IS - 2051-1426 (Linking) VI - 9 IP - 7 DP - 2021 Jul TI - First-in-human DR5 PET reveals insufficient DR5 expression in patients with gastrointestinal cancer. LID - 10.1136/jitc-2021-002926 [doi] LID - e002926 AB - 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 (89)Zr-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 (18)F-FDG and (89)Zr-CTB006 PET/CT. The tumor tissues were obtained through surgical operation and DR5 expression levels were confirmed by RNAscope. RESULTS: Preclinical studies showed that (89)Zr-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 (89)Zr-CTB006 with a mean maximum standardized uptake value (SUV(max)) of 6.63+/-3.29 (range 1.8-13.8). Tumor tissue was obtained from 18 patients, and (89)Zr-CTB006 uptake in patients with RNAscope scores of 3-4 was significantly higher than that in patients with scores of 0-2. An SUV(max) 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: (89)Zr-CTB006 PET/CT is capable of detecting DR5 expression in cancer patients and is a promising approach to screen patients with DR5 overexpression. CI - (c) Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Wang, Shujing AU - Wang S AD - Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China. AD - NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Beijing, China. AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. FAU - Zhu, Hua AU - Zhu H AD - Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China. AD - NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Beijing, China. AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. FAU - Li, Yingjie AU - Li Y AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. AD - Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Ding, Jin AU - Ding J AD - Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China. AD - NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Beijing, China. AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. FAU - Wang, Feng AU - Wang F AD - Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China. AD - NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Beijing, China. AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. FAU - Ding, Lixin AU - Ding L AD - Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China. AD - NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Beijing, China. AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. FAU - Wang, Xinyu AU - Wang X AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. AD - Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Zhao, Jun AU - Zhao J AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. AD - Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Zhang, Yan AU - Zhang Y AD - Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China. AD - NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Beijing, China. AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. FAU - Yao, Yunfeng AU - Yao Y AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. AD - Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Zhou, Tong AU - Zhou T AD - Department of Cell Biology and Divisions of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA. FAU - Li, Nan AU - Li N AD - Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China rainbow6283@sina.com wuaw@sina.com pekyz@163.com. AD - NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Beijing, China. AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. FAU - Wu, Aiwen AU - Wu A AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China rainbow6283@sina.com wuaw@sina.com pekyz@163.com. AD - Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Yang, Zhi AU - Yang Z AUID- ORCID: 0000-0003-2084-5193 AD - Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China rainbow6283@sina.com wuaw@sina.com pekyz@163.com. AD - NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Beijing, China. AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Immunother Cancer JT - Journal for immunotherapy of cancer JID - 101620585 RN - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand) RN - 0 (TNFRSF10B protein, human) SB - IM MH - Cell Line, Tumor MH - Female MH - Gastrointestinal Neoplasms/*diagnostic imaging/*genetics MH - Humans MH - Positron Emission Tomography Computed Tomography/*methods MH - Receptors, TNF-Related Apoptosis-Inducing Ligand/*metabolism PMC - PMC8728342 OTO - NOTNLM OT - immunologic OT - receptors OT - tumor biomarkers COIS- Competing interests: No, there are no competing interests. EDAT- 2021/07/25 06:00 MHDA- 2022/01/12 06:00 PMCR- 2021/07/22 CRDT- 2021/07/24 05:40 PHST- 2021/06/25 00:00 [accepted] PHST- 2021/07/24 05:40 [entrez] PHST- 2021/07/25 06:00 [pubmed] PHST- 2022/01/12 06:00 [medline] PHST- 2021/07/22 00:00 [pmc-release] AID - jitc-2021-002926 [pii] AID - 10.1136/jitc-2021-002926 [doi] PST - ppublish SO - J Immunother Cancer. 2021 Jul;9(7):e002926. doi: 10.1136/jitc-2021-002926.