Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
Laboratory of Biophysical Chemistry, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan.
Mol Pharm. 2024 Nov 4;21(11):5728-5735. doi: 10.1021/acs.molpharmaceut.4c00732. Epub 2024 Oct 24.
In this study, thermosensitive liposomes (TSLs) encapsulating urinary excretable radiolabeled compounds were developed. We considered that the release of the radiolabeled compounds from the TSLs in the blood by heating the blood in peripheral tissues can achieve rapid clearance of radioactivity, resulting in improved imaging contrast. To demonstrate the hypothesis, classical TSLs mainly composed of 1,2-dipalmitoyl--glycero-3-phosphocholine with a phase transition temperature of 41 °C were used. The optimal composition of TSLs was determined by an in vitro release test using [In]In-diethylenetriaminepentaacetic acid (DTPA)-encapsulated liposomes, which showed that the cholesterol content drastically changed the release characteristics of classical TSLs. In the biodistribution experiments, [In]In-DTPA was significantly released from the TSLs in the blood when the tails of mice were heated at 43 °C. The tumor-to-blood ratio of the heated group was three times higher than that of the nonheated group, and accumulation in normal tissues of the heated group was lower than that of the nonheated group. These results demonstrate the usefulness of the method using TSLs to encapsulate urinary excretable radiolabeled compounds for improving imaging contrast.
在这项研究中，开发了一种包裹可随尿液排出的放射性标记化合物的温敏脂质体（TSL）。我们认为，通过加热外周组织中的血液，可使血液中的 TSL 释放出放射性标记化合物，从而实现放射性快速清除，提高成像对比度。为了验证这一假设，使用相变温度为 41°C 的主要由 1,2-二棕榈酰基-sn-甘油-3-磷酸胆碱组成的经典 TSL。通过使用[In]In-二乙三胺五乙酸（DTPA）包裹的脂质体进行的体外释放试验确定了 TSL 的最佳组成，结果表明胆固醇含量极大地改变了经典 TSL 的释放特性。在生物分布实验中，当用 43°C 加热小鼠尾巴时，[In]In-DTPA 从 TSL 中大量释放出来。加热组的肿瘤与血液的比值是未加热组的三倍，且加热组在正常组织中的积累量低于未加热组。这些结果表明，使用 TSL 来包裹可随尿液排出的放射性标记化合物的方法在提高成像对比度方面是有用的。
