Development\nof Radiolabeled Probes with Improved Imaging\nContrast by Releasing Urinary Excretable Radiolabeled Compounds from\nThermosensitive Liposomes in the Blood

In this study, thermosensitive liposomes\n(TSLs) encapsulating\nurinary\nexcretable radiolabeled compounds were developed. We considered that\nthe release of the radiolabeled compounds from the TSLs in the blood\nby heating the blood in peripheral tissues can achieve rapid clearance\nof radioactivity, resulting in improved imaging contrast. To demonstrate\nthe hypothesis, classical TSLs mainly composed of 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine with a phase transition temperature\nof 41 °C were used. The optimal composition of TSLs was determined\nby an in vitro release test using [<sup>111</sup>In]In-diethylenetriaminepentaacetic\nacid (DTPA)-encapsulated liposomes, which showed that the cholesterol\ncontent drastically changed the release characteristics of classical\nTSLs. In the biodistribution experiments, [<sup>111</sup>In]In-DTPA\nwas significantly released from the TSLs in the blood when the tails\nof mice were heated at 43 °C. The tumor-to-blood ratio of the\nheated group was three times higher than that of the nonheated group,\nand accumulation in normal tissues of the heated group was lower than\nthat of the nonheated group. These results demonstrate the usefulness\nof the method using TSLs to encapsulate urinary excretable radiolabeled\ncompounds for improving imaging contrast.