Multimodal Imaging Technology Effectively Monitors HER2 Expression in Tumors Using Trastuzumab-Coupled Organic Nanoparticles in Patient-Derived Xenograft Mice Models.
Multimodal Imaging Technology Effectively Monitors HER2 Expression in Tumors Using Trastuzumab-Coupled Organic Nanoparticles in Patient-Derived Xenograft Mice Models.
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多模态成像技术在患者来源的异种移植小鼠模型中使用曲妥珠单抗偶联的有机纳米颗粒有效监测肿瘤中 HER2 的表达
DOI：
10.3389/fonc.2021.778728
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhu H
中科院分区：
文献类型：
--
作者：
Wen L;Xia L;Guo X;Huang HF;Wang F;Yang XT;Yang Z;Zhu H
曲妥珠单抗是一种靶向人表皮生长因子2（HER 2）的单克隆抗体，已成功用于乳腺癌和胃癌患者的治疗，但仍存在心脏毒性、耐药性和疗效不可预测等问题。在此，我们构建了一种新型的有机多巴胺-黑色素纳米颗粒（dMNs）作为载体，然后表面负载曲妥珠单抗，构建了一个多功能的纳米探针命名为Her-PEG-dMNPs。我们使用micro-PET/CT和PET/MRI多模态成像来评价在标记放射性核素64 Cu或124 I和MRI造影剂Mn 2+后，纳米探针在胃癌患者来源的异种移植（PDX）小鼠模型中HER 2表达中的保留效应。纳米探针可以在体外特异性靶向表达HER 2的SKOV-3细胞（3.61 ± 0.74 vs. 1.24 ± 0.43，2 h，P = 0.002）。在体内，micro-PET/CT和PET/MRI显示124 I标记的纳米探针在PDX模型中具有比作为载体的未负载dMNP更大的对比度和保留效果（在24小时时1.63 ± 0.07对0.90 ± 0.04，P = 0.002），在64 Cu标记的Her-PEG-dMNP中发现了相似性。由于124 I具有较长的半衰期并且与纳米颗粒的药代动力学相匹配，因此我们专注于124 I-Her-PEG-dMNP的进一步评价。此外，免疫组织化学染色证实了HER 2在动物模型中的过表达。本研究开发并验证了用于定量小鼠中HER 2表达的新型HER 2特异性多模态成像纳米探针。通过对肿瘤部位的强保留作用，可用于单克隆抗体治疗效果的促进和过程监控。
Trastuzumab is a monoclonal antibody targeting human epidermal growth factor 2 (HER2), which has been successfully used in the treatment of patients with breast cancer and gastric cancer; however, problems concerning its cardiotoxicity, drug resistance, and unpredictable efficacy still remain. Herein, we constructed novel organic dopamine–melanin nanoparticles (dMNs) as a carrier and then surface-loaded them with trastuzumab to construct a multifunctional nanoprobe named Her-PEG-dMNPs. We used micro-PET/CT and PET/MRI multimodality imaging to evaluate the retention effect of the nanoprobe in HER2 expression in gastric cancer patient-derived xenograft (PDX) mice models after labeling of the radionuclides 64Cu or 124I and MRI contrast agent Mn2+. The nanoprobes can specifically target the HER2-expressing SKOV-3 cells in vitro (3.61 ± 0.74 vs. 1.24 ± 0.43 for 2 h, P = 0.002). In vivo, micro-PET/CT and PET/MRI showed that the 124I-labeled nanoprobe had greater contrast and retention effect in PDX models than unloaded dMNPs as carrier (1.63 ± 0.07 vs. 0.90 ± 0.04 at 24 h, P = 0.002), a similarity found in 64Cu-labeled Her-PEG-dMNPs. Because 124I has a longer half-life and matches the pharmacokinetics of the nanoparticles, we focused on the further evaluation of 124I-Her-PEG-dMNPs. Furthermore, immunohistochemistry staining confirmed the overexpression of HER2 in the animal model. This study developed and validated novel HER2-specific multimodality imaging nanoprobes for quantifying HER2 expression in mice. Through the strong retention effect of the tumor site, it can be used for the promotion of monoclonal antibody treatment effect and process monitoring.
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DOI：
10.1007/s00259-011-1768-2
发表时间：
2011-05
影响因子：
9.1
作者：
Lubberink, Mark;Herzog, Hans
通讯作者：
Herzog, Hans
影响因子：
56.9
作者：
SLAMON, DJ;CLARK, GM;MCGUIRE, WL
通讯作者：
MCGUIRE, WL
影响因子：
8.4
作者：
Sun Y;Hong S;Ma X;Cheng K;Wang J;Zhang Z;Yang M;Jiang Y;Hong X;Cheng Z
通讯作者：
Cheng Z
影响因子：
3.2
作者：
Lee I;Lim I;Byun BH;Kim BI;Choi CW;Woo SK;Kim KI;Lee KC;Kang JH;Seong MK;Kim HA;Noh WC;Lim SM
通讯作者：
Lim SM
将生物标志物转移到分子探针中：黑色素纳米颗粒作为多模态成像的天然活性平台
影响因子：
15
作者：
Fan Q;Cheng K;Hu X;Ma X;Zhang R;Yang M;Lu X;Xing L;Huang W;Gambhir SS;Cheng Z
通讯作者：
Cheng Z