Rhein‐based necrosis‐avid MRI contrast agents for early evaluation of tumor response to microwave ablation therapy

摘要

Purpose Early evaluation of tumor response to thermal ablation therapy can help identify untreated tumor cells and then perform repeated treatment as soon as possible. The purpose of this work was to explore the potential of rhein‐based necrosis‐avid contrast agents (NACAs) for early evaluation of tumor response to microwave ablation (MWA). Methods 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide (MTT) assay was performed to test the cytotoxicity of rhein‐based NACAs against HepG2 cells. Rat models of liver MWA were used for investigating the effectiveness of rhein‐based NACAs in imaging the MWA lesion, the optimal time period for post‐MWA MRI examination, and the metabolic behaviors of 68 Ga‐labeled rhein‐based NACAs. Rat models of orthotopic liver W256 tumor MWA were used for investigating the time window of rhein‐based NACAs for imaging the MWA lesion, the effectiveness of these NACAs in distinguishing the residual tumor and the MWA lesion, and their feasibility in early evaluating the tumor response to MWA. Results Gadolinium 2,2',2''‐(10‐(2‐((4‐(4,5‐Dihydroxy‐9,10‐dioxo‐9,10‐dihydroanthracene‐2‐carboxamido)butyl)amino)‐2‐oxoethyl)‐1,4,7,10‐tetraazacyclododecane‐1,4,7‐triyl)triacetic acid (GdL 2 ) showed low cytotoxicity and high quality in imaging the MWA region. The optimal time period for post‐MWA MRI examination using GdL 2 was 2 to 24 h after the treatment. During 2.5 to 3.5 h postinjection, GdL 2 can better visualize the MWA lesion in comparison with gadolinium 2‐[4,7,10‐tris(carboxymethyl)‐1,4,7,10‐tetraazacyclododec‐1‐yl]acetic acid (Gd‐DOTA), and the residual tumor would not be enhanced. The tumor response to MWA as evaluated by using GdL 2 ‐enhanced MRI was consistent with histological examination. Conclusion GdL 2 appears to be a promising NACA for the tumor response assessment after thermal ablation therapies.