ArticleEuropean journal of nuclear medicine and molecular imaging2026
Minimal chemical modification enables alpha/beta radiolabeling of sacituzumab govitecan for targeted therapy in high grade serous ovarian cancer.
Article in European journal of nuclear medicine and molecular imaging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeOvarian cancer (OC) is frequently diagnosed at late stages after metastasis and chemorefractive leading to poor survival outcomes. There is a critical need for earlier detection and novel antigen-targeted therapies to improve patient survival at all stages. TROP-2 is a transmembrane glycoprotein overexpressed in many cancers and presents a promising target for OC. Recently, antibody-drug conjugates such as sacituzumab govitecan (SG) and datopotamab deruxtecan have been approved for various TROP-2-positive malignancies such as metastatic breast, lung, or urothelial cancer. However, diagnosis is based on prior therapy failure and TROP-2 therapy focused on antibody-drug conjugates.
methodsMinimal radiotheranostic versions of SG were developed for immunoPET imaging with [89Zr]Zr-DFO-SG in flank and intraperitoneal OVCAR3 implants. IHC was also done to identify other OC models that express Trop2. Radiotherapy variants of SG [177Lu]Lu-DTPA-SG, [225Ac]Ac-mcp-Direct-SG, or [225Ac]Ac-mcp-Click-SG were also made and tested for efficacy alongside the standard of care SG.
results[177Lu]Lu-DTPA-SG delayed tumor recurrence for up 6–8 weeks post-treatment and retreatment prolonged overall survival to 21 weeks matching standard of care SG dosing. Between two linkers, [225Ac]Ac-mcp-Direct-SG was found to yield a superior minimal conjugation of SG than [225Ac]Ac-mcp-Click-SG, with better tumor targeting by biodistribution and prolonged reduction in OC over 30 weeks.
conclusionUltimately, utility of SG was improved through minimal modification of the ADC and applied a “treat what you see” approach to TROP-2-positive OC. By using a new tetrafluorophenyl linkage of macropa, [225Ac]Ac-mcp-Direct-SG greatly reduced tumor burden in OC with most mice surviving and tolerating the therapy.
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