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

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 (Tc-99m)-sestamibi exhibited the lowest heart uptake the blood pool and delayed images compared to both Tc-99m-liposomal agents. Liver and spleen uptake in the control samples with Tc-99m-sestamibi increased in 1-h-delayed images, unlike with Tc-99m-liposomal agents, which were decreased in delayed images. The mean maximum count in the bladder for Tc-99m-sestamibi loaded liposomes 1 h post-injection was 2354.6 (+/- 2.6%) compared to 178.4 (+/- 0.54%) for Tc-99m-sestamibi without liposomes. Liposomal encapsulation reduced the cytotoxic effect of the sestamibi. Tc-99m-MIBI-cationic liposomes exhibited excellent early uptake and clearance compared to Tc-99m-MIBI without liposomes. Adding cholesterol during liposome formation enhanced the stability and specificity of the targeted organs.

Automated summary

The aim of this study was to develop a suitable method for encapsulating a tracer in liposomes to enhance the stability and efficacy of radiopharmaceuticals. The results showed that liposomal encapsulation reduced uptake and retention of the drug in unintended organs, and also reduced its cytotoxic effect. Adding cholesterol during the formulation process enhanced the stability and specificity of the targeted organs.