Effective Treatment of SSTR2-Positive Small Cell Lung Cancer Using 211At-Containing Targeted α-Particle Therapy Agent Which Promotes Endogenous Antitumor Immune Response
机构：[1]Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, Shanghai 200072, People's Republic of China.[2]Institute of Nuclear Medicine, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, Shanghai 200072, People's Republic of China.[3]Key Laboratory of Radiation Physics and Technology, Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610064, People's Republic of China.
Small cell lung cancer (SCLC) is a neuroendocrine tumor with a high degree of malignancy. Due to limited treatment options, patients with SCLC have a poor prognosis. We have found, however, that intravenously administered octreotide (Oct) armed with astatine-211 ([211At]SAB-Oct) is effective against a somatostatin receptor 2 (SSTR2)-positive SCLC tumor in SCLC tumor-bearing BALB/c nude mice. In biodistribution analysis, [211At]SAB-Oct achieved the highest concentration in the SCLC tumors up to 3 h after injection as time proceeded. A single intravenous injection of [211At]SAB-Oct (370 kBq) was sufficient to suppress SSTR2-positive SCLC tumor growth in treated mice by inducing DNA double-strand breaks. Additionally, a multitreatment course (370 kBq followed by twice doses of 370 kBq for a total of 1110 kBq) inhibited the growth of the tumor compared to the untreated control group without significant off-target toxicity. Surprisingly, we found that [211At]SAB-Oct could up-regulate the expressions of calreticulin and major histocompatibility complex I (MHC-I) on the tumor cell membrane surface, suggesting that α-particle internal irradiation may activate an endogenous antitumor immune response through the regulation of immune cells in the tumor microenvironment, which could synergically enhance the efficacy of immunotherapy. We conclude that [211At]SAB-Oct is a potential new therapeutic option for SSTR2-positive SCLC.
基金：
This research was funded by the National Natural Science
Foundation of China (82071956), and the Shanghai Anti-
Cancer Association (SACA-CY22C05).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|2 区医学
小类|2 区药学3 区医学：研究与实验
最新[2023]版：
大类|2 区医学
小类|2 区药学3 区医学：研究与实验
第一作者：
第一作者机构：[1]Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, Shanghai 200072, People's Republic of China.[2]Institute of Nuclear Medicine, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, Shanghai 200072, People's Republic of China.
通讯作者：
通讯机构：[1]Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, Shanghai 200072, People's Republic of China.[2]Institute of Nuclear Medicine, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, Shanghai 200072, People's Republic of China.
推荐引用方式(GB/T 7714)：
Qin Shanshan,Yang Yuanyou,Zhang Jiajia,et al.Effective Treatment of SSTR2-Positive Small Cell Lung Cancer Using 211At-Containing Targeted α-Particle Therapy Agent Which Promotes Endogenous Antitumor Immune Response[J].Molecular pharmaceutics.2023,doi:10.1021/acs.molpharmaceut.3c00427.
APA：
Qin Shanshan,Yang Yuanyou,Zhang Jiajia,Yin Yuzhen,Liu Weihao...&Yu Fei.(2023).Effective Treatment of SSTR2-Positive Small Cell Lung Cancer Using 211At-Containing Targeted α-Particle Therapy Agent Which Promotes Endogenous Antitumor Immune Response.Molecular pharmaceutics,,
MLA：
Qin Shanshan,et al."Effective Treatment of SSTR2-Positive Small Cell Lung Cancer Using 211At-Containing Targeted α-Particle Therapy Agent Which Promotes Endogenous Antitumor Immune Response".Molecular pharmaceutics .(2023)
