Trophoblast cell surface antigen 2(Trop2)has been widely characterized as a clinically significant pan-cancer biomarker expressed in various tumors,significantly impacting tumor growth,invasion,and metastasis.In this ...Trophoblast cell surface antigen 2(Trop2)has been widely characterized as a clinically significant pan-cancer biomarker expressed in various tumors,significantly impacting tumor growth,invasion,and metastasis.In this study,we develop Trop2 targeting peptide-based radiotracer[^(68)Ga]Ga-NOTA-GL10 for accurately detecting the Trop2 expression levels through positron emission tomography(PET)imaging.The Trop2-targeting peptide GL10 was rationally designed through computational methods based on the T2-2 peptide,and conjugated with the 1,4,7-triazacyclononane-N,N′,N″-triacetic acid(NOTA)chelator to synthesize the precursor NOTA-GL10 with nanomolar affinity for Trop2(K_(D)=12.9 nM).The radiosynthesis of[^(68)Ga]Ga-NOTA-GL10 was achieved via conventional methods with high radiochemical yield(RCY),good stability,and favorable pharmacokinetics.Dynamic PET imaging revealed that the tracer presented a significantly higher tumor uptake((5.03±0.49)%ID/mL)and tumor-to-muscle ratio(4.44±0.30)in Trop2-positive BxPC-3 xenografts compared to that in Trop2-negative PANC-1 xenografts((1.41±0.13)%ID/mL,1.23±0.27).Moreover,near-infrared(NIR)fluorescence imaging of the probe ICG-GL10 further confirmed the ability of GL10 to specifically target Trop2-positive tumors.The peptide-based Trop2 targeting radiotracer[^(68)Ga]Ga-NOTA-GL10 demonstrated high specificity and sensitivity in detecting Trop2 expression,which revealed the potential of Trop2-based non-invasive imaging for cancer diagnosis.展开更多
基金supported by the National Natural Science Foundation of China(22407052)the Jiangsu Provincial Natural Science Foundation(BK20240300)+4 种基金the Scientific Research Project of Jiangsu Commission of Health(MQ2024007,H2023150,K2024007)the Wuxi Science and Technology Development Fund(K20241060)the Major Project of Wuxi Municipal Health Commission(Z202303)the Wuxi Association for Science and Technology(TJXD-2024-102)the Jiangsu Province Capability Improvement Project through Science,Technology and Education(ZDXYS202211)。
文摘Trophoblast cell surface antigen 2(Trop2)has been widely characterized as a clinically significant pan-cancer biomarker expressed in various tumors,significantly impacting tumor growth,invasion,and metastasis.In this study,we develop Trop2 targeting peptide-based radiotracer[^(68)Ga]Ga-NOTA-GL10 for accurately detecting the Trop2 expression levels through positron emission tomography(PET)imaging.The Trop2-targeting peptide GL10 was rationally designed through computational methods based on the T2-2 peptide,and conjugated with the 1,4,7-triazacyclononane-N,N′,N″-triacetic acid(NOTA)chelator to synthesize the precursor NOTA-GL10 with nanomolar affinity for Trop2(K_(D)=12.9 nM).The radiosynthesis of[^(68)Ga]Ga-NOTA-GL10 was achieved via conventional methods with high radiochemical yield(RCY),good stability,and favorable pharmacokinetics.Dynamic PET imaging revealed that the tracer presented a significantly higher tumor uptake((5.03±0.49)%ID/mL)and tumor-to-muscle ratio(4.44±0.30)in Trop2-positive BxPC-3 xenografts compared to that in Trop2-negative PANC-1 xenografts((1.41±0.13)%ID/mL,1.23±0.27).Moreover,near-infrared(NIR)fluorescence imaging of the probe ICG-GL10 further confirmed the ability of GL10 to specifically target Trop2-positive tumors.The peptide-based Trop2 targeting radiotracer[^(68)Ga]Ga-NOTA-GL10 demonstrated high specificity and sensitivity in detecting Trop2 expression,which revealed the potential of Trop2-based non-invasive imaging for cancer diagnosis.
