PMID- 36039398 OWN - NLM STAT- MEDLINE DCOM- 20221004 LR - 20221019 IS - 1543-8392 (Electronic) IS - 1543-8384 (Linking) VI - 19 IP - 10 DP - 2022 Oct 3 TI - Immuno-PET Imaging of TNF-alpha in Colitis Using (89)Zr-DFO-infliximab. PG - 3632-3639 LID - 10.1021/acs.molpharmaceut.2c00411 [doi] AB - Tumor necrosis factor-alpha (TNF-alpha) neutralization has become increasingly important in the treatment of inflammatory bowel diseases (IBD). A series of monoclonal antibodies were approved in the clinic for anti-TNF-alpha therapy. However, a comprehensive assessment of TNF-alpha levels throughout the colon, which facilitates the diagnosis of IBD and predicts anti-TNF-alpha efficacy, remains challenging. Here, we radiolabeled infliximab with long-lived radionuclides (89)Zr for immuno-positron emission tomography (PET) imaging of TNF-alpha in vivo. The increased TNF-alpha level was detected in the inflammatory colon of the dextran sodium sulfate-induced colitis mice. The immuno-PET imaging of (89)Zr-desferrioxamine-infliximab reveals a high uptake (7.1 +/- 0.3%ID/g) in the inflammatory colon, which is significantly higher than in the healthy control and blocked groups. The colon-to-muscle ratio reached more than 10 and was maintained at a high level for 10 h after injection. The ex vivo biodistribution study also verified the superior uptake in the inflammatory colon. This study provides an in vivo immune-PET approach to molecular imaging of the pro-inflammatory cytokine TNF-alpha. It is promising in diagnosing and predicting efficacy in both IBD and other autoimmune diseases. FAU - Yan, Ge AU - Yan G AD - School of Pharmacy, Nanjing Medical University, Nanjing 211166, PR China. AD - NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, PR China. FAU - Wang, Xinyu AU - Wang X AUID- ORCID: 0000-0002-9167-2077 AD - School of Pharmacy, Nanjing Medical University, Nanjing 211166, PR China. AD - NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, PR China. FAU - Fan, Yeli AU - Fan Y AD - College of Environmental Engineering, Wuxi University, Wuxi 214105, PR China. FAU - Lin, Jianhan AU - Lin J AD - School of Pharmacy, Nanjing Medical University, Nanjing 211166, PR China. AD - NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, PR China. FAU - Yan, Junjie AU - Yan J AUID- ORCID: 0000-0001-8016-2277 AD - School of Pharmacy, Nanjing Medical University, Nanjing 211166, PR China. AD - NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, PR China. FAU - Wang, Lizhen AU - Wang L AD - NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, PR China. FAU - Pan, Donghui AU - Pan D AD - NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, PR China. FAU - Xu, Yuping AU - Xu Y AD - School of Pharmacy, Nanjing Medical University, Nanjing 211166, PR China. AD - NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, PR China. FAU - Yang, Min AU - Yang M AUID- ORCID: 0000-0001-6976-8526 AD - School of Pharmacy, Nanjing Medical University, Nanjing 211166, PR China. AD - NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, PR China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220829 PL - United States TA - Mol Pharm JT - Molecular pharmaceutics JID - 101197791 RN - 0 (Antibodies, Monoclonal) RN - 0 (Dextrans) RN - 0 (Radioisotopes) RN - 0 (Tumor Necrosis Factor Inhibitors) RN - 0 (Tumor Necrosis Factor-alpha) RN - B72HH48FLU (Infliximab) RN - C6V6S92N3C (Zirconium) RN - J06Y7MXW4D (Deferoxamine) SB - IM MH - Animals MH - Antibodies, Monoclonal MH - Cell Line, Tumor MH - *Colitis/chemically induced/diagnostic imaging/drug therapy MH - Deferoxamine MH - Dextrans MH - *Inflammatory Bowel Diseases MH - Infliximab MH - Mice MH - Positron-Emission Tomography/methods MH - Radioisotopes MH - Tissue Distribution MH - Tumor Necrosis Factor Inhibitors MH - Tumor Necrosis Factor-alpha MH - Zirconium OTO - NOTNLM OT - PET imaging OT - TNF-alpha OT - inflammatory bowel diseases OT - infliximab OT - zirconium-89 EDAT- 2022/08/31 06:00 MHDA- 2022/10/05 06:00 CRDT- 2022/08/30 01:53 PHST- 2022/08/31 06:00 [pubmed] PHST- 2022/10/05 06:00 [medline] PHST- 2022/08/30 01:53 [entrez] AID - 10.1021/acs.molpharmaceut.2c00411 [doi] PST - ppublish SO - Mol Pharm. 2022 Oct 3;19(10):3632-3639. doi: 10.1021/acs.molpharmaceut.2c00411. Epub 2022 Aug 29.