Kit formulation for the preparation of radioactive blue liposomes for sentinel node lymphoscintigraphy.
A radioactively labeled blue liposome formulation was developed for use in presurgical lymphoscintigraphy and intraoperative sentinel node localization to avoid the differing injection site clearance kinetics of the conjunctive use of separate formulations of low molecular weight blue dye and radioactively labeled macromolecular sulfur colloid. Blue liposomes containing glutathione in the internal aqueous phase were prepared from blue dyed lipids obtained by covalently binding Reactive Blue II to phosphatidylethanolamine (PE) fractions of phospholipid extracts. Four phospholipid extracts with differing PE fractions and a centrifugation technique were evaluated with the goal of maximizing the blue color intensity of the formulation. Stability of the formulations was evaluated by studying radiolabeling efficiency (using a membrane permeable lipophilic carrier of the commonly used diagnostic radionuclide, technetium-99m) and particle-size distribution over 30-60-day periods. Blue color was not altered by varying the PE content, while centrifugation was an effective and convenient method to maximize the blue color intensity of the final preparation. The particle size distribution of the prepared liposomes ranged from 200-300 nm (considered ideal for lymphoscintigraphy studies) and did not change significantly, while radiolabeling efficiency exceeded 80% for up to 1 month. The described kit formulation for the preparation of radiolabeled blue liposomes is suitable for commercial production allowing widespread clinical use. The combination of a means of visual identification and tracking of the liposomes through the lymphatic channels along with the ability to trace the preparation using standard radiation detection instrumentation provides the surgeon with an improved radiolabeled compound for lymphoscintigraphy and intraoperative sentinel lymph node identification.
Division of Pharmacy Practice & Administration, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
Edward M
EM
Plut
George H
GH
Hinkle
Wenjin
W
Guo
Robert J
RJ
Lee
D004353:Drug Evaluation, Preclinical / Q000379:methods; D004355:Drug Stability; D008081:Liposomes / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D008198:Lymph Nodes / Q000000981:diagnostic imaging* / Q000601:surgery; D010316:Particle Size; D011877:Radionuclide Imaging / Q000379:methods; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000493:pharmacokinetics; D011933:Reagent Kits, Diagnostic / Q000592:standards; D021701:Sentinel Lymph Node Biopsy; D013667:Technetium / Q000737:chemistry; D014227:Triazines / Q000737:chemistry*
D008081:Liposomes; D019275:Radiopharmaceuticals; D011933:Reagent Kits, Diagnostic; D014227:Triazines; C012842:Cibacron Blue F 3GA; D013667:Technetium