Enhanced Efficacy of Radiopharmaceuticals When Using Technetium-99m-Labeled Liposomal Agents: Synthesis and Pharmacokinetic Properties

使用锝-99m标记的脂质体制剂可提高放射性药物的疗效:合成和药代动力学特性

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Abstract

Challenges posed by the retention of radiopharmaceuticals in unintended organs affect the quality of patient procedures when undergoing diagnostics and therapeutics. The aim of this study was to formulate a suitable tracer encapsulated in liposomes using different techniques and compounds to enhance the stability, uptake, clearance, and cytotoxic effect of the radiopharmaceutical. Cationic liposomes were prepared by a thin-film method using dipalmitoyl phosphatidylcholine (DPPC) and cholesterol. Whole-body gamma camera images were acquired of intravenously injected New Zealand rabbits. Additionally, liposomes were assessed using stability, toxicity, zeta potential, and particle size tests. In the control cases, Technetium-99m ((99m)Tc)-sestamibi exhibited the lowest heart uptake the blood pool and delayed images compared to both (99m)Tc-liposomal agents. Liver and spleen uptake in the control samples with (99m)Tc-sestamibi increased in 1-h-delayed images, unlike with (99m)Tc-liposomal agents, which were decreased in delayed images. The mean maximum count in the bladder for (99m)Tc-sestamibi loaded liposomes 1 h post-injection was 2354.6 (±2.6%) compared to 178.4 (±0.54%) for (99m)Tc-sestamibi without liposomes. Liposomal encapsulation reduced the cytotoxic effect of the sestamibi. (99m)Tc-MIBI-cationic liposomes exhibited excellent early uptake and clearance compared to (99m)Tc-MIBI without liposomes. Adding cholesterol during liposome formation enhanced the stability and specificity of the targeted organs.

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