Liang Xie, Jialin Qin, Cuiping Song, Jianchun Yin, Ruixue Wu, Hong Chen, Yujie Dong, Nianfei Wang, Lei Chen, Bing Hong, Ni Chen, Peng Lu, Fei Li, Xiaoxi Pang
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引用次数: 0
Abstract
Purpose: Gadolinium-neutron capture therapy (Gd-NCT) employs isotopically enriched Gadolinium (Gd) and thermal neutrons to selectively target cancer cells. This study investigated the targeting efficacy of 157Gd-DOTA-PSMA (Prostate-Specific Membrane Antigen) in prostate cancer and explored its potential applications in Gd-NCT.
Methods and results: We developed 157Gd-DOTA-PSMA, a novel theranostic bio-gadolinium agent specifically designed for magnetic resonance imaging (MRI)-guided Gd-NCT. 68 Ga-DOTA-PSMA positron emission tomography-computed tomography (PET/CT) imaging showed peak radiotracer uptake at 2 h post-injection, with a tumor-to-non-tumor (T/NT) ratio of 6.95 ± 0.60. MRI analysis confirmed a stable T1 signal enhancement 2 h post-injection. Time-of-flight inductively coupled plasma mass spectrometry (TOF-ICP-MS) revealed significantly elevated Gd concentrations in 22Rv1 tumor compared to PC-3 tumor and other healthy organs. ICP-MS analysis showed Gd concentrations of 165.69 μg [Gd]/g in 22Rv1 tumors and 35.25 μg [Gd]/g in blood, yielding a tumor-to-blood (T/B) ratio of 4.65 ± 0.54 and a T/NT ratio of 3.65 ± 0.49. Neutron irradiation with 157Gd-DOTA-PSMA reduced cell viability, inhibited colony formation, and induced DNA damage and apoptosis in 22Rv1 cells. In 22Rv1 mice, γ-H2AX levels peaked at 6 h post-irradiation, accompanied by an increase in pro-apoptotic proteins and a decrease in anti-apoptotic proteins over 24 h. In the NCT group following the injection of 157Gd-DOTA-PSMA, there was effective suppression of tumor growth without a loss of body weight, resulting in a 1.7-fold increase in median survival compared to control group.
Conclusions: 157Gd-DOTA-PSMA, as a theranostic bio-gadolinium agent designed for targeted Gd-NCT in prostate cancer, represents a novel therapeutic approach and broadens the scope of potential applications of neutron capture therapy.
期刊介绍:
The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses.
The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.