Department of Health Technology, Technical University of Denmark, Produktionstorvet Building 423, DK 2800 Lyngby, Denmark.
Center for Nanomedicine and Theranostics, Technical University of Denmark, 2800 Lyngby, Denmark.
Nanotheranostics. 2020 Apr 22;4(3):142-155. doi: 10.7150/ntno.44562. eCollection 2020.
Liquid brachytherapy is an emerging technology for internal radiation therapy where liquids containing radionuclides are administered directly into solid tumors. These technologies are less invasive than conventional brachytherapy, and can potentially improve the dose coverage and homogeneity of the radioactivity distribution within the tumor. For this purpose, we have developed a novel cationic micelle system for delivery of a range of radionuclides. The system is applicable for emitters of alpha, beta or photon radiation, and enables dose-mapping via theranostic nuclear imaging. The cationic micelles were developed as linear surfactants comprising the chelator DOTA, a triarginine sequence and a palmitoyl or stearoyl fatty acid chain. The critical micelle concentration of the surfactants was determined, and the micelles were radiolabelled with Cu or Lu in high radiochemical purity (>95%). The tumor retention and biodistribution of the Cu-radiolabeled surfactants, administered as micelles or formulated in liposomes, were investigated by PET/CT in a tumor bearing mouse model. The interaction of the micelles with anionic lipid membranes was demonstrated to be favourable, using a liposome partition assay. , the surfactants formulated both as cationic micelles and liposomes displayed the best intratumoral retention, with micelles providing more homogeneous activity distribution. A cationic, surfactant-based drug delivery system was developed and demonstrated promise as a vehicle for liquid brachytherapy when formulated as micelles or in liposomes. The system enables accurate dosimetry due to the flexible radiochemistry of DOTA.
液体近距离治疗是一种新兴的内部放射治疗技术，其中含有放射性核素的液体直接施用于实体肿瘤。这些技术比传统近距离治疗侵入性更小，并且有可能改善肿瘤内放射性分布的剂量覆盖和均匀性。为此，我们开发了一种用于递送一系列放射性核素的新型阳离子胶束系统。该系统适用于α、β或光子辐射发射体，并能够通过治疗核成像进行剂量测绘。阳离子胶束被开发为线性表面活性剂，包括螯合剂 DOTA、三精氨酸序列和棕榈酰或硬脂酰脂肪酸链。测定了表面活性剂的临界胶束浓度，并以高放射化学纯度（>95%）用 Cu 或 Lu 对胶束进行放射性标记。通过 PET/CT 在荷瘤小鼠模型中研究了作为胶束或包封在脂质体中的 Cu 放射性标记的表面活性剂的肿瘤保留和生物分布。使用脂质体分配测定法证明了胶束与阴离子脂质膜的相互作用是有利的。胶束或脂质体形式的表面活性剂都显示出最好的肿瘤内保留，胶束提供了更均匀的活性分布。已经开发了一种基于阳离子表面活性剂的药物递送系统，并证明了当作为胶束或脂质体配制时，它有希望成为液体近距离治疗的载体。由于 DOTA 的灵活放射化学性质，该系统能够实现精确的剂量测定。
