ArticleMolecular imaging and biology2025
Evaluation of Indocyanine Green Derivatives with Sulfonic Acid and Carboxylic Acid Groups at the Benzoindolenine Moiety for Antibody-Based Tumor Imaging.
Article in Molecular imaging and biology, 2025. 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
purposeIn target-specific cancer imaging, antibodies and their fragments are conjugated with fluorescent dyes to work as targeting molecules. We have recently developed indocyanine green (ICG) derivatives with anionic functional groups at the benzoindolenine moiety. When the ICG derivatives are used for antibody-based imaging, the chemical characteristics of the conjugated dyes may influence the pharmacokinetics of the targeting molecules. Therefore, in this study, we evaluated the in vivo pharmacokinetics of IgG and Fab conjugated with the ICG derivatives bearing anionic functional groups. PROCEDURES: A linker for conjugation was introduced into the methine chain of ICG and ICG derivatives possessing sulfonic acid (SC-Cy) or carboxylic acid (CC-Cy) groups at the benzoindolenine moiety. ICG, SC-Cy, or CC-Cy was conjugated with IgG, innate trastuzumab, and its Fab fragment. To evaluate the pharmacokinetics of these IgG-dyes and Fab-dyes, in vivo fluorescence imaging was performed in tumor-bearing mice at 0.25-96 h after intravenous administration of the imaging agents.
resultsThe three IgG-dyes exhibited similar pharmacokinetics and tumor accumulation profiles post injection. Thus, the differences in the dye's chemical properties had minimal influence when the ICG derivatives were conjugated with IgG. In contrast, the pharmacokinetics and tumor accumulation profiles of the Fab-dyes were remarkably different. While Fab-SC-Cy exhibited high accumulation in the kidney but no accumulation in the tumors, Fab-CC-Cy showed higher tumor accumulation. This could be attributed to the excessively high negative charge density in the benzoindolenine moiety of SC-Cy, which influenced the excretion route of the Fab fragment.
conclusionsThe IgG conjugated with SC-Cy or CC-Cy dyes exhibited favorable pharmacokinetics profiles. In contrast, Fab-CC-Cy demonstrated superior performance in tumor imaging compared to Fab-SC-Cy. Our findings suggest that introducing anionic functional groups into the benzoindolenine moiety of ICG could lead to the development of near-infrared dyes that could be useful in antibody-based tumor imaging.
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