Development of Radiolabeled Probes with Improved Imaging Contrast by Releasing Urinary Excretable Radiolabeled Compounds from Thermosensitive Liposomes in the Blood

被引：0

作者：

Munekane, Masayuki ^{[1
,2
]}

Ozaki, Miki ^{[1
]}

Mitani, Yuri ^{[1
]}

Sakaida, Natsuki ^{[2
]}

Sano, Kohei ^{[2
]}

Yamasaki, Toshihide ^{[2
]}

Mukai, Takahiro ^{[2
]}

Mishiro, Kenji ^{[3
]}

Fuchigami, Takeshi ^{[1
]}

Ogawa, Kazuma ^{[1
,3
]}

机构：

[1] Kanazawa Univ, Grad Sch Med Sci, Kanazawa, Ishikawa 9201192, Japan

[2] Kobe Pharmaceut Univ, Lab Biophys Chem, Kobe 6588558, Japan

[3] Kanazawa Univ, Inst Frontier Sci Initiat, Kanazawa 9201192, Japan

来源：

MOLECULAR PHARMACEUTICS | 2024年 / 21卷 / 11期

关键词：

thermosensitive liposomes; In-111-diethylenetriaminepentaaceticacid; drug release; imaging contrast; cholesterol; radiotheranostics; TUMOR; RADIOTHERANOSTICS; PHARMACOKINETICS; CHOLESTEROL; THERAPY;

D O I：

10.1021/acs.molpharmaceut.4c00732

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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-sn-glycero-3-phosphocholine with a phase transition temperature of 41 degrees C were used. The optimal composition of TSLs was determined by an in vitro release test using [111In]In-diethylenetriaminepentaacetic acid (DTPA)-encapsulated liposomes, which showed that the cholesterol content drastically changed the release characteristics of classical TSLs. In the biodistribution experiments, [111In]In-DTPA was significantly released from the TSLs in the blood when the tails of mice were heated at 43 degrees 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.

引用

页码：5728 / 5735

页数：8