title: Radiolabeling and targeting of lipidic nanocapsules for applications in radioimmunotherapy.
abstract: OBJECTIVE
  Radioimmunotherapy is limited in some cases by the low radioactive doses delivered to tumor cells by antibodies or pretargeted haptens. In order to increase this dose, lipidic nanocapsules (LNC) with a hydrophobic core are proposed as radionuclide vectors that could be targeted to cancer cells by a bispecific anti-tumor x anti-hapten antibody after incorporation of different haptens in the nanocapsule membrane.
  
  
  METHODS
  To bind different radionuclides to the nanocapsules, several bifunctional chelating agents (BCA) were used to form stable complexes with the radionuclides. Some of them are hydrophilic for LNC shell while others are lipophilic to radiolabel the core. Poly(ethylene glycols) (PEG) were used to increase the residence time in blood. Since PEG can modify haptens recognition by the bispecific antibody and radiolabeling efficiency, haptens, BCA or Bolton-Hunter reagent (BH) were attached to the PEG extremity to optimize accessibility. Specific constructs (DSPE-PEG-haptens, DSPE-PEG-BCA, and DSPE-PEG-BH) were synthesized to develop these new radiolabeled vector formulations. Large amounts of PEG have been introduced by a postinsertion method without important change in nanocapsule size and properties. The nanocapsule core was radiolabeled with a lipophilic [(99m)Tc]SSS complex.
  
  
  RESULTS
  Serum stability studies showed that this (99m)Tc-labeling method was efficient for at least 20 h. Concerning the nanocapsule surface, several methods have been performed for (111)In-labeling by using DSPE-PEG-DTPA and for (125)I-labeling with DSPE-PEG-BH.
  
  
  CONCLUSIONS
  The nanocapsules labeling feasibility with a variety of radionuclides and their stability were demonstrated in this paper.
authors: INSERM, U 601, University of Nantes, Nantes, France.
authors: E
authors: E
authors: Jestin
authors: M
authors: M
authors: Mougin-Degraef
authors: A
authors: A
authors: Faivre-Chauvet
authors: P
authors: P
authors: Remaud-Le Saëc
authors: F
authors: F
authors: Hindre
authors: J P
authors: JP
authors: Benoit
authors: J F
authors: JF
authors: Chatal
authors: J
authors: J
authors: Barbet
authors: J F
authors: JF
authors: Gestin
mesh_terms: D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D005240:Feasibility Studies; D007553:Isotope Labeling / Q000379:methods*; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D053769:Nanocapsules; D011868:Radioisotopes