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用于乳腺癌成像的纳米放射性药物:在诱导动物中的研发、表征及成像

Nanoradiopharmaceuticals for breast cancer imaging: development, characterization, and imaging in inducted animals.

作者信息

Sarcinelli Michelle Alvares, Albernaz Marta de Souza, Szwed Marzena, Iscaife Alexandre, Leite Kátia Ramos Moreira, Junqueira Mara de Souza, Bernardes Emerson Soares, da Silva Emerson Oliveira, Tavares Maria Ines Bruno, Santos-Oliveira Ralph

机构信息

Instituto de Macromoléculas Professora Eloisa Mano Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Laboratory of Medical Investigation, Faculty of Medicine, São Paulo University, São Paulo, Brazil.

Radiopharmacy Sector, University Hospital Clementino Fraga Filho, Rio de Janeiro, Brazil.

出版信息

Onco Targets Ther. 2016 Sep 23;9:5847-5854. doi: 10.2147/OTT.S110787. eCollection 2016.

Abstract

Monoclonal antibodies as polymeric nanoparticles are quite interesting and endow this new drug category with many advantages, especially by reducing the number of adverse reactions and, in the case of radiopharmaceuticals, also reducing the amount of radiation (dose) administered to the patient. In this study, a nanoradiopharmaceutical was developed using polylactic acid (PLA)/polyvinyl alcohol (PVA)/montmorillonite (MMT)/trastuzumab nanoparticles labeled with technetium-99m (99mTc) for breast cancer imaging. In order to confirm the nanoparticle formation, atomic force microscopy and dynamic light scattering were performed. Cytotoxicity of the nanoparticle and biodistribution with 99mTc in healthy and inducted animals were also measured. The results from atomic force microscopy showed that the nanoparticles were spherical, with a size range of ~200-500 nm. The dynamic light scattering analysis demonstrated that over 90% of the nanoparticles produced had a size of 287 nm with a zeta potential of -14,6 mV. The cytotoxicity results demonstrated that the nanoparticles were capable of reaching breast cancer cells. The biodistribution data demonstrated that the PLA/PVA/MMT/trastuzumab nanoparticles labeled with 99mTc have great renal clearance and also a high uptake by the lesion, as ~45% of the PLA/PVA/MMT/trastuzumab nanoparticles injected were taken up by the lesion. The data support PLA/PVA/MMT/trastuzumab labeled with 99mTc nanoparticles as nanoradiopharmaceuticals for breast cancer imaging.

摘要

作为聚合物纳米颗粒的单克隆抗体非常有趣,赋予了这一新药类别诸多优势,特别是减少了不良反应的数量,对于放射性药物而言,还减少了给予患者的辐射量(剂量)。在本研究中,开发了一种纳米放射性药物,它是用聚乳酸(PLA)/聚乙烯醇(PVA)/蒙脱石(MMT)/曲妥珠单抗纳米颗粒标记锝 - 99m(99mTc)用于乳腺癌成像。为了确认纳米颗粒的形成,进行了原子力显微镜和动态光散射分析。还测量了纳米颗粒在健康动物和诱导动物中的细胞毒性以及99mTc的生物分布。原子力显微镜的结果表明,纳米颗粒呈球形,尺寸范围约为200 - 500 nm。动态光散射分析表明,超过90%的所产生纳米颗粒尺寸为287 nm,zeta电位为 - 14.6 mV。细胞毒性结果表明,纳米颗粒能够到达乳腺癌细胞。生物分布数据表明,标记有99mTc的PLA/PVA/MMT/曲妥珠单抗纳米颗粒具有良好的肾脏清除率,并且病变部位摄取率高,因为注射的PLA/PVA/MMT/曲妥珠单抗纳米颗粒约45%被病变部位摄取。这些数据支持标记有99mTc的PLA/PVA/MMT/曲妥珠单抗纳米颗粒作为用于乳腺癌成像的纳米放射性药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/253e/5045224/e73118b28091/ott-9-5847Fig1.jpg

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