Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
Nanoscale. 2019 Aug 1;11(30):14400-14409. doi: 10.1039/c9nr04371c.
Somatostatin receptor subtype 2 (SSTR2) is highly expressed in pulmonary neuroendocrine tumors, which account for approximately 25% of all lung cancers including small-cell lung cancer (SCLC). It is possible to establish SCLC-specific imaging agents for multimodal imaging to obtain tumor integrity information. Herein, we constructed novel multifunctional organic melanin nanoparticles (MNPs) as a carrier and surface-loaded somatostatin analog octreotide to produce a human small-cell lung cancer-targeted nanoprobe OCT-PEG-MNPs. MNPs have an excellent photoacoustic imaging (PAI) function and can be directly chelated with the magnetic resonance contrast agent Mn2+, and N-bromo succinimide (NBS) can be used as an oxidant to label the nanoparticles with the long half-life radionuclide 124I by an electrophilic substitution reaction. Therefore, (124I, Mn) OCT-PEG-MNPs can not only be used for PAI but also be used for positron emission tomography (PET) and magnetic resonance imaging (MRI). The NCI-H69 SCLC tumor xenograft model with high SSTR2 expression was constructed to evaluate the multimodal imaging ability of (124I, Mn) OCT-PEG-MNPs. This nanoprobe showed good imaging abilities in PAI, MRI and PET. The PA images showed that the photoacoustic signal in the NCI-H69 tumor site gradually increased with time, and the NCI-H69 xenograft showed a clear increase in the T1-weighted signal intensity after injection of Mn-OCT-PEG-MNPs at 24 h compared to that in the prescan. MicroPET and biodistribution studies showed that the uptake of NCI-H69 tumors (8.03 ± 0.37% ID g-1) was significantly higher than that in the control A549 model (3.35 ± 0.54% ID g-1) after injection of (124I, Mn) OCT-PEG-MNPs at 24 h. The (124I, Mn) OCT-PEG-MNPs were successfully applied to multimodal imaging in a small-cell lung cancer model with high SSTR2 expression. This nanoprobe may be considered for clinical trials since it combines the numerous advantages of organic nanoparticles.
生长抑素受体亚型 2（SSTR2）在肺神经内分泌肿瘤中高度表达，约占所有肺癌（包括小细胞肺癌[SCLC]）的 25%。有可能建立 SCLC 特异性成像剂，用于多模态成像以获得肿瘤完整性信息。在此，我们构建了新型多功能有机黑色素纳米颗粒（MNPs）作为载体，并表面负载生长抑素类似物奥曲肽，以产生针对人小细胞肺癌的靶向纳米探针 OCT-PEG-MNPs。MNPs 具有优异的光声成像（PAI）功能，可直接螯合磁共振对比剂 Mn2+，N-溴代琥珀酰亚胺（NBS）可用作氧化剂，通过亲电取代反应用长半衰期放射性核素 124I 标记纳米颗粒。因此，（124I，Mn）OCT-PEG-MNPs 不仅可用于 PAI，还可用于正电子发射断层扫描（PET）和磁共振成像（MRI）。构建了高 SSTR2 表达的 NCI-H69 SCLC 肿瘤异种移植模型，以评估（124I，Mn）OCT-PEG-MNPs 的多模态成像能力。该纳米探针在 PAI、MRI 和 PET 中表现出良好的成像能力。PA 图像显示，NCI-H69 肿瘤部位的光声信号随时间逐渐增加，与预扫描相比，注射 Mn-OCT-PEG-MNPs 24 h 后，NCI-H69 异种移植的 T1 加权信号强度明显增加。MicroPET 和生物分布研究表明，注射（124I，Mn）OCT-PEG-MNPs 24 h 后，NCI-H69 肿瘤的摄取量（8.03±0.37%ID g-1）明显高于对照 A549 模型（3.35±0.54%ID g-1）。（124I，Mn）OCT-PEG-MNPs 成功应用于高 SSTR2 表达的小细胞肺癌模型的多模态成像。由于该纳米探针结合了有机纳米颗粒的众多优势，因此可以考虑用于临床试验。
