EPR-Mediated Colon Cancer Imaging with a Novel Tc-99m-Imatinib Nanosystem: In Vivo Evaluation and Computational Dosimetric Characterization
Makaleler > Tam Makale · 2026
Yazarlar: Emre ÖZGENÇ, Evren ATLIHAN GÜNDOĞDU, Yücel BAŞPINAR, Umit Kara, Ozge Kilicoglu
Current Pharmaceutical Design, Uluslararası, Wos, 2026, cilt 32
DOI: 10.2174/0113816128493313260701092444
Özet
Introduction/Objectives: This study aimed to develop a Technetium-99m-labeled nano-structured lipid carrier (Tc-99m-IMT-NSLC) system for passive targeted imaging of colon cancer and to theoretically characterize its dosimetric properties using computational modeling. Methods: Nano-Structured Lipid Carriers (NSLCs) loaded with Imatinib were prepared and radiolabeled with Tc-99m. The system underwent physicochemical characterization, in vitro stability, and in vivo SPECT imaging, pharmacokinetic, and biodistribution studies using male Balb-C-Nude mice with HCT-116 colon cancer xenografts. Simultaneously, the Mass Attenuation Coefficients (MACs) of relevant tissues (colon, small intestine, stomach) were determined using MATLAB-based numerical modeling benchmarked against the WinXCOM database. results: The 99mTc-IMT-NSLC exhibited an optimal particle size (173.05 ± 9 nm) and high stability (> 92% radiochemical purity after 6 hours). The pharmacokinetic profile of the NSLC system showed a significantly lower elimination rate (ke : 0.92 h−1) compared to the free solution (ke : 3.02 h−1), leading to a 3.3-fold increase in Mean Residence Time (M RT ) and a 2.4-fold higher Area Under the Curve (AU C) (p < 0.05). This enhanced circulation enabled a 5.6-fold higher tumor-to-non-target (T /N T ) uptake ratio at 2 hours post-injection. Monte Carlo simulations accurately characterized tissue-specific radiation attenuation, showing a strong correlation with established databases (deviation ≤ 2.5%). Results: The Tc-99m-IMT-NSLC nanocarrier was synthesized with an Imatinib loading efficiency of 85.5% ± 3.2% and a radiochemical yield exceeding 90%. The system demonstrated high stability, maintaining a Radiochemical Purity (RCP) exceeding 92% after 6 hours of plasma incubation. The Tc-99m-IMT-NSLC showed a superior pharmacokinetic profile, evidenced by a 3.3-fold increase in Mean Residence Time MRT and a 2.4- fold higher Area Under the Curve AUC compared to the free solution. This passive targeting resulted in a 5.6- fold higher Tumor-to-Non-Target (T/NT) uptake ratio at 2 hours post-injection. The simulations successfully determined the radiation attenuation coefficients for the tissues investigated. Discussion: The superior pharmacokinetic profile and tumor uptake of the Tc-99m-IMT-NSLC formulation validate the effectiveness of the NSLC platform in exploiting the Enhanced Permeability and Retention (EPR) effect for passive tumor targeting. The results demonstrate that the nanocarrier design effectively protects the payload from rapid clearance, thereby enhancing signal contrast in SPECT/CT. By integrating experimental imaging data with computational dosimetric modeling, this study highlights the necessity of using tissuespecific attenuation parameters to ensure accurate quantification in nuclear medicine. These findings confirm the dual utility of the proposed system: it functions as a highly specific diagnostic tracer while providing a foundational dosimetric framework for future transition toward theranostic applications and therapeutic radiopharmaceutical planning. Conclusion: The developed Tc-99m-IMT-NSLC system is a promising, stable nanocarrier for colon cancer imaging. Its success in overcoming the limitations of free-drug pharmacokinetics, combined with the precision offered by the established dosimetric simulation data, supports its potential for further clinical translation and more sophisticated dosimetric evaluations in radiopharmaceutical therapy.