Noninvasive molecular imaging using anti-Trop-2 aptamer for targeted therapy of small cell lung cancer

作者：Yamei Chen, Xuwei Liu, Yang Sun, Keying Liu, Ding Ding, Shaoli Song, Weihong Tan · 发表于：Journal of Nanobiotechnology · 年份：2025 · DOI：10.1186/s12951-025-03184-6 · 被引用次数：11 · 研究领域：Lung Cancer Research Studies、Advanced biosensing and bioanalysis techniques、Peptidase Inhibition and Analysis

Recent advancements in antibody-drug conjugates (ADCs) targeting trophoblast surface cell antigen 2 (Trop-2) have brought important progress in the field of targeted therapy. This progress also holds promise for the treatment of small cell lung cancer (SCLC) as anti-Trop-2 therapy appears to have a safe and effective clinical activity in metastatic SCLC patients. However, effective treatments of anti-Trop-2 ADCs rely on the comprehensive assessment of Trop-2 expression at the tumor sites, SCLC exhibits intratumoral heterogeneity, making the accurate acquisition of histological biopsies a challenge. To address this issue, we herein report the development of an anti-Trop-2 aptamer consisting of 76 bases is specifically bind to Trop-2-overexpressing SCLC cells. Further truncated anti-Trop-2 aptamer with 46 nucleotides also possesses excellent in vitro and in vivo binding affinity with Trop-2 antigens. After radiolabeling with gallium-68 radionuclide, an aptamer-based molecular imaging probe was successfully fabricated named [68Ga]Ga-NOTA-TRP-c. This imaging probe demonstrated effective and precise differentiation of Trop-2-positive tumors in both murine- and human-derived animal models, exhibiting favorable metabolic profiles. Furthermore, Trop-2-positive SCLC tumors recognized by anti-Trop-2 aptamer can be treated with anti-Trop-2 ADC sacituzumab govitecan (SG), either in vitro or in vivo. Importantly, SG induces DNA damage and cell apoptosis without affecting the expression of...