机构：[1]Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, China. rongtiannuclear@126.com.四川大学华西医院[2]Department of Nuclear Medicine and Clinical Nuclear Medicine Research Lab, West China Hospital, Sichuan University, Chengdu, China.四川大学华西医院[3]Nuclear Power Institute of China, National Engineering Research Center of Isotope and Medicine, and Radioisotope Engineering Technology Research Center of Sichuan, Chengdu, China.[4]Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.[5]Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Malignant tumors pose substantial treatment challenges due to their heterogeneity, metastatic potential, and therapeutic resistance, underscoring the urgent need for more effective treatment options. In this study, a novel radionuclide drug conjugate (RDC) was developed and characterized employing a tumor-targeting heptamethine carbocyanine dye (DZ) for its high specificity and favourable safety profile. The RDC, DOTA-DZ-HX, was synthesized by conjugating DZ with dodecane tetraacetic acid (DOTA) through a dipeptide linker. The anti-tumor efficacy and biodistribution of [177Lu]Lu-DOTA-DZ-HX were assessed in H1975 and HeLa xenograft models. [177Lu]Lu-DOTA-DZ-HX showed high stability, specific tumor accumulation, and substantial radioactivity retention at the tumor site for seven days. Biodistribution analysis revealed that the drug exhibited prolonged blood circulation with gradual clearance. Additionally, [177Lu]Lu-DOTA-DZ-HX could effectively and selectively inhibit tumor growth, as evidenced by a significant reduction in tumor volume. These findings suggest that heptamethine carbocyanine dye-directed radionuclide targeting could provide an effective treatment for cancer and potentially other malignancies, representing a significant advancement in cancer therapy.
基金：
This work was supported by the National Natural Science
Foundation of China (Grant No. 82472022).
语种：
外文
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出版当年[2024]版：
无
最新[2023]版：
大类|3 区医学
小类|3 区材料科学：生物材料
第一作者：
第一作者机构：[1]Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, China. rongtiannuclear@126.com.
共同第一作者：
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推荐引用方式(GB/T 7714)：
Huang Mingxing,Wang Weichen,Wang Yingwei,et al.Advancing cancer therapy with a heptamethine carbocyanine dye-conjugated radionuclide drug[J].Journal Of Materials Chemistry. B.2024,doi:10.1039/d4tb01798f.
APA：
Huang Mingxing,Wang Weichen,Wang Yingwei,Wang Rang,Pan Lili...&Tian Rong.(2024).Advancing cancer therapy with a heptamethine carbocyanine dye-conjugated radionuclide drug.Journal Of Materials Chemistry. B,,
MLA：
Huang Mingxing,et al."Advancing cancer therapy with a heptamethine carbocyanine dye-conjugated radionuclide drug".Journal Of Materials Chemistry. B .(2024)
