Radiolabeling of liposome-encapsulated amikacin (LEA) with Tc-99m

1526 Objectives LEA (Arikace®), an antibiotic (amikacin ,70mg/ml) encapsulated liposome, is an investigational drug developed for inhalation therapy of lung infection. To 1) optimize Tc-99m labeling parameters to yield a high labeling efficiency without a significant impact on the liposome size and stability and 2) develop analytical methods to determine the labeling efficiency and stability of Tc-99m LEA. Methods LEA (0.4ml in 1.5%NaCl) was reacted with 99mTc (30mCi 99mTcO4-/0.02ml of 1.5%NaCl) using SnCl2 (0.02ml of 2.2mM) dissolved in HCl or ascorbic acid as a reducing agent for 10min at 22 °C. The labeled products were then purified by anion exchange resin. The purified Tc-99m LEA in 1.5%NaCl solution was incubated at 4 and 22 °C to assess its stability with ITLC, paper chromatography, centrifugal filtration, and low pressure liquid chromatography (LPLC). The purified Tc-99m LEA was subjected to studies by a clinical nebulization instrument (PARI eFlow®) and the Anderson Cascade Impactor (ACI). Results The labeling reaction appeared to increase the viscosity of LEA when the HCl concentration was ~1mM. On the other hand, the use of ascorbic acid at 1 mM resulted in a high labeling efficiency (>92%), and there was Conclusions The labeling method using SnCl2 in 1 mM ascorbic acid produced Tc-99m LEA with a high labeling efficiency and stability