title: (99m)Tc-labeled therapeutic inhaled amikacin loaded liposomes.
abstract: The radiolabeling of the liposome surface can be a useful tool for in vivo tracking of therapeutic drug loaded liposomes. We investigated radiolabeling therapeutic drug (i.e. an antibiotic, amikacin) loaded liposomes with (99m)Tc, nebulization properties of (99m)Tc-labeled liposomal amikacin for inhalation ((99m)Tc-LAI), and its stability by size exclusion low-pressure liquid chromatography (LPLC). LAI was reacted with (99m)Tc using SnCl2 dissolved in ascorbic acid as a reducing agent for 10 min at room temperature. The labeled products were then purified by anion exchange resin. The purified (99m)Tc-LAI in 1.5% NaCl solution was incubated at 4 °C to assess its stability by LPLC. The purified (99m)Tc-LAI was subjected to studies with a clinically used nebulizer (PARI eFlow®) and the Anderson Cascade Impactor (ACI). The use of ascorbic acid at 0.91 mM resulted in a quantitative labeling efficiency. The LPLC profile showed that the liposomal peak of LAI detected by a UV monitor at both 200 nm and 254 nm overlapped with the radioactivity peak of (99m)Tc-LAI, indicating that (99m)Tc-LAI is suitable for tracing LAI. The ACI study demonstrated that the aerosol droplet size distribution determined gravimetrically was similar to that determined by radioactivity. The liposome surface labeling method using SnCl₂ in 0.91 mM ascorbic acid produced (99m)Tc-LAI with a high labeling efficiency and stability that are adequate to evaluate the deposition and clearance of inhaled LAI in the lung by gamma scintigraphy.
authors.affiliation: Radiopharmaceutical Laboratory, Division of Nuclear Medicine, Department of Radiology and Imaging Sciences, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda , MD 20892 , USA .
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Kenneth T
authors.initials: KT
authors.lastname: Cheng
authors.forename: Vladimir
authors.initials: V
authors.lastname: Malinin
authors.forename: Zhili
authors.initials: Z
authors.lastname: Li
authors.forename: Zhengsheng
authors.initials: Z
authors.lastname: Yao
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Christine M
authors.initials: CM
authors.lastname: Gould
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Olivier
authors.forename: Clara
authors.initials: C
authors.lastname: Chen
authors.forename: Walter R
authors.initials: WR
authors.lastname: Perkins
authors.forename: Chang H
authors.initials: CH
authors.lastname: Paik
mesh_terms: D000280:Administration, Inhalation; D000583:Amikacin / Q000008:administration & dosage* / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D008081:Liposomes; D015609:Organotechnetium Compounds / Q000737:chemistry*; D010316:Particle Size; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000900:Anti-Bacterial Agents; D008081:Liposomes; D015609:Organotechnetium Compounds; D000583:Amikacin