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Multimodality labeling of NGR-functionalized hyaluronan for tumor targeting and radiotherapy.

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机构： [1]Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, 646000 Luzhou, China [2]Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, 621900 Mianyang, China [3]Collaborative Innovation Center of Radiation Medicine of Jiangsu, Higher Education Institutions, 215123 Suzhou, China [4]Key Laboratory of Nuclear Medicine and Molecular Imaging of Sichuan Province, 621999 Mianyang, China

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关键词： 177Lu labeling Fluorescence probe Aminopeptidase N Hyaluronan Tumor targeting

摘要：

Hyaluronan (HA) is a negatively charged linear polysaccharide that can interact with cluster determinant 44 (CD44) overexpressed cancers. However, HA can also bind to excess substrates in the human body leading to the lower specificity of tumor targeting. Conjugation of other targeting group to HA could enhance the uptake by cancer cell comparing to that of native HA. In this study, we develop the multi-functionalized HA (177Lu-DOTA/Alexa647-HA100-N) for malignant tumor targeting. An asparagine-glycine-arginine (NGR) based peptide was selected for HA functionalization. The peptide is known to target CD13 receptor that is overexpressed in malignant tumors with abundant blood vessels, such as lung cancer. Furthermore, the fluorescent probe Alexa Fluor 647 for ex vivo/in vivo tracking and the radionuclide 177Lu for radioactive therapy were both labeled on the material. The functionalized HA could be bound by lung cancer cells and breast cancer cells. In vivo fluorescent imaging showed that the material could accumulate in the tumor site for more than 96 h. The 177Lu labeling of functionalized HA was stable for more 48 h at physiological conditions. The accumulation of 177Lu-DOTA/Alexa647-HA100-N in the tumor of lung cancer (NCI-H292) bearing mice was 1.91±0.97%ID/g, and it was about 17 times higher than the value in blood. Conclusion: The multimodality labeled functional HA was successfully prepared and could be fluorescent trackable ex vivo and in vivo. It showed high potential to be used for malignant cancer radiotherapy for its specific targeting property to tumors and radiotoxicity from the labeled 177Lu radionuclide. Copyright © 2021. Published by Elsevier B.V.

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出版当年[2021]版：

大类 | 2 区医学

小类 | 2 区药学

最新[2023]版：

大类 | 3 区医学

小类 | 2 区药学

第一作者：

第一作者机构： [1]Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, 646000 Luzhou, China [2]Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, 621900 Mianyang, China

通讯作者：

通讯机构： [1]Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, 646000 Luzhou, China [2]Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, 621900 Mianyang, China [3]Collaborative Innovation Center of Radiation Medicine of Jiangsu, Higher Education Institutions, 215123 Suzhou, China [4]Key Laboratory of Nuclear Medicine and Molecular Imaging of Sichuan Province, 621999 Mianyang, China

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