Noninvasive molecular imaging using anti-Trop-2 aptamer for targeted therapy of small cell lung cancer
Abstract 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 t...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-03-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-025-03184-6 |
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| Summary: | Abstract 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 Trop-2 on the cell surface, which makes it possible to use anti-Trop-2 aptamer to monitor the expression of Trop-2 in SCLC. This study highlights the potential of aptamer-based molecular imaging and imaging-guided SG treatment as a promising option for targeted therapy in SCLC. Graphical Abstract |
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| ISSN: | 1477-3155 |