Comparative analysis of the efficacy and safety of antibody‑drug conjugates, radionuclide‑drug conjugates and their combination targeting claudin 18.2 in gastric cancer treatment
机构：[1]Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan 621000, P.R. China[2]National Health Commission Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan 621000, P.R. China[3]Sichuan Clinical Research Center for Radiation and Therapy, Mianyang Central Hospital, Mianyang, Sichuan 621000, P.R. China[4]Department of Nuclear Medicine, Central Hospital of Mianyang, Mianyang, Sichuan 621000, P.R. China[5]Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang, Sichuan 621900, P.R. China[6]Targeted Radiopharmaceuticals Creation Key Laboratory of Sichuan Province, Mianyang, Sichuan 621900, P.R. China[7]Department of Clinical Medicine, Clinical Medical School, North Sichuan Medical College, Nanchong, Sichuan 637007, P.R. China
Gastric cancer (GC) is one of the most common types of cancer worldwide, with limited therapeutic options available for patients with advanced‑stage disease. Claudin 18.2 (CLDN18.2) has emerged as a popular target for the diagnosis and treatment of GC. Although antibody‑drug conjugates (ADCs) and radionuclide‑drug conjugates (RDCs) targeting CLDN18.2 have been assessed, to the best of our knowledge, no comparative studies have evaluated the efficacy and toxicity profiles of these two treatment modalities. The present study aimed to compare the antitumor efficacy and toxicity of ADCs and RDCs derived from the same anti‑CLDN18.2 monoclonal antibody (mAb) targeting CLDN18.2‑positive tumors. Modified DFO/DOTA‑SYSA1801mAb, labeled with 89Zr and 177Lu, was used in cell‑based assays, positron emission tomography and biodistribution studies to evaluate its targeting specificity. In an NUGC‑4‑CLDN18.2 xenograft tumor model, the antitumor efficacy and toxicity of the mAb (SYSA1801mAb), as well as the ADC (SYSA1801) and RDC ([177Lu]Lu‑DOTA‑SYSA1801mAb), and their combinations in different sequences (ADC→RDC and RDC→ADC), were systematically assessed. [89Zr]Zr‑DFO‑SYSA1801mAb demonstrated notable in vitro stability and effectively imaged tumors with high CLDN18.2 expression. [177Lu]Lu‑DOTA‑SYSA1801mAb exhibited strong tumor‑targeting ability, with significantly higher tumor uptake than other tissues. By day 145, the complete remission (CR) rate in the ADC group was 60%, with an overall survival (OS) rate of 60%. In the ADC→RDC group, the CR and OS rates were both 40%. The OS rates in the RDC, RDC→ADC, mAb and control groups were all 0%. The ADC group exhibited minimal changes in hematological parameters and hepatic/renal function, whereas the RDC and RDC→ADC groups showed more significant changes. These preclinical findings suggested that ADC monotherapy may demonstrate superior efficacy and safety profiles when compared with RDC monotherapy. Furthermore, sequential combination therapy that starts with ADC appears to be more favorable than approaches that start with RDC. Although ADC→RDC sequential therapy did not significantly outperform ADC monotherapy in this model, it may serve as an effective subsequent treatment strategy.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2026]版：
无
最新[2025]版：
大类|3 区医学
小类|4 区肿瘤学
第一作者：
第一作者机构：[1]Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan 621000, P.R. China[2]National Health Commission Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan 621000, P.R. China
通讯作者：
通讯机构：[1]Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan 621000, P.R. China[2]National Health Commission Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan 621000, P.R. China[3]Sichuan Clinical Research Center for Radiation and Therapy, Mianyang Central Hospital, Mianyang, Sichuan 621000, P.R. China[5]Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang, Sichuan 621900, P.R. China[6]Targeted Radiopharmaceuticals Creation Key Laboratory of Sichuan Province, Mianyang, Sichuan 621900, P.R. China
推荐引用方式(GB/T 7714)：
Du Huan,Hao Xiao-Fei,Lin Bin-Wei,et al.Comparative analysis of the efficacy and safety of antibody‑drug conjugates, radionuclide‑drug conjugates and their combination targeting claudin 18.2 in gastric cancer treatment[J].Oncology Reports.2026,55(1):doi:10.3892/or.2025.9009.
APA：
Du Huan,Hao Xiao-Fei,Lin Bin-Wei,Zhang Yu,Rui Luo...&Du Xiaobo.(2026).Comparative analysis of the efficacy and safety of antibody‑drug conjugates, radionuclide‑drug conjugates and their combination targeting claudin 18.2 in gastric cancer treatment.Oncology Reports,55,(1)
MLA：
Du Huan,et al."Comparative analysis of the efficacy and safety of antibody‑drug conjugates, radionuclide‑drug conjugates and their combination targeting claudin 18.2 in gastric cancer treatment".Oncology Reports 55..1(2026)
