Therapeutic efficacy and imaging assessment of the HER2-targeting chemotherapy drug ZHER2:V2-pemetrexed in lung adenocarcinoma Xenografts

被引：7

作者：

Han, Jingya ^{[1
]}

Zhao, Yan ^{[2
]}

Zhao, Xinming ^{[1
]}

Ma, Tuo ^{[1
]}

Hao, Tiancheng ^{[1
]}

Liu, Jiahui ^{[1
]}

Zhang, Zhaoqi ^{[1
]}

Zhang, Jingmian ^{[1
]}

Wang, Jianfang ^{[1
]}

机构：

[1] Hebei Med Univ, Dept Nucl Med, Hosp 4, Jiankang Rd, Shijiazhuang 050011, Hebei, Peoples R China

[2] Hebei Med Univ, Dept Oncol, Hosp 4, Shijiazhuang 050011, Hebei, Peoples R China

来源：

INVESTIGATIONAL NEW DRUGS | 2020年 / 38卷 / 04期

基金：

中国国家自然科学基金;

关键词：

HER2; Affibody; Tc-99m-Z(HER2); V2-pemetrexed; Molecular imaging; Pemetrexed; Therapeutic response; PHASE-III; IN-VITRO; CANCER; HER2; CISPLATIN; CYTOTOXICITY; EXPRESSION; BLOCKADE;

D O I：

10.1007/s10637-019-00876-3

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Chemotherapy has always been the first therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) with untreatable oncogenic mutations. However, chemotherapy has demonstrated limited success and is associated with severe side effects. This research aimed to investigate the antitumor efficacy and cytotoxic safety of the conjugate Z(HER2:V2)-pemetrexed, a novel targeted chemotherapeutic drug. In this context, human epidermal growth factor receptor 2 (HER2) + A549 lung xenografts were treated using Z(HER2:V2)-pemetrexed, pemetrexed or physiological saline. Therapeutic efficacy was monitored by single photon emission computed tomography (SPECT) imaging using the Tc-99m-labeled Z(HER2:V2)-pemetrexed conjugate and further confirmed by performing apoptosis assays using flow cytometry analysis and hematoxylin-eosin (H&E) staining. To evaluate the expression of HER2 in tumor tissues, immunohistochemistry was performed, accompanied by quantitative analysis using flow cytometry. A toxicological evaluation was also conducted. Imaging with Tc-99m-Z(HER2:V2)-pemetrexed demonstrated that in HER2+ A549 models, Z(HER2:V2)-pemetrexed showed better antineoplastic effects than pemetrexed. Compared with pemetrexed, the results from the pathological and flow cytometry analyses also revealed that Z(HER2:V2)-pemetrexed exhibits high antitumor activity against A549 tumors, inducing necrosis, apoptosis and cell cycle arrest. In addition, the clinical signs of toxicity in the Z(HER2:V2)-pemetrexed treated group were reduced compared with those in the pemetrexed treated group. These data revealed that the Z(HER2:V2)-pemetrexed conjugate encompasses promising targeted antitumor activity against HER2-positive lung adenocarcinoma, with reduced side effects compared with pemetrexed. Thus, the Z(HER2:V2)-pemetrexed conjugate may serve as a novel molecular agent with tremendous clinical breakthrough potential in the diagnosis and treatment of HER2-positive lung adenocarcinoma.

引用

页码：1031 / 1043

页数：13

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