title: Preclinical evaluation of technetium 99m-labeled P1827DS for infection imaging and comparison with technetium 99m IL-8.
abstract: BACKGROUND
  The technetium 99 m (99mTc)-radiolabeled, leukocyte-avid peptide-glycoseaminoglycan complex, [99mTc]P1827DS, has been synthesized as an improved infection/inflammation imaging agent to [99mTc]P483H (LeukoTect, Diatide). In a phase I/II clinical trail, [99mTc]P483H images were equivalent to those obtained with 111In ex vivo labeled leukocytes. However, there was physiologic accumulation of radioactivity in the body that could hamper interpretation of the images. In this study, the potential of [99mTc]P1827DS for infection imaging was assessed in comparison with [99mTc]P483H and the well-described imaging agent [99mTc] hydrazinonicotinamide (HYNIC)-interleukin 8 (IL-8).
  
  
  METHODS
  The binding of [99mTc]P1827DS to human blood cell was studied in vitro. A rabbit Escherichia coli infection model was used to perform the biodistribution and imaging studies with [99mTc]P1827DS, [99mTc]P483H and [99mTc]HYNIC-IL-8.
  
  
  RESULTS
  [99mTc]P1827DS binds to leukocytes but not to erythrocytes. The leukocyte binding was not saturable up to an investigated concentration of 10 microM. The accumulation of [99mTc]P1827/DS at the infection site strongly depends on the P1827/DS ratio and was optimal at a molar ratio of 10:1. [99mTc]P1827DS shows improved biodistribution over [99mTc]P483H with similar uptake at the infection site. Abscess uptake of [99mTc]HYNIC-IL-8 was approximately three times higher than that of [99mTc]P1827DS. [99mTc]HYNIC-IL-8 showed high accumulation in the kidneys, whereas [99mTc]P1827DS showed high lung uptake and slightly higher accumulation in the liver and spleen.
  
  
  CONCLUSIONS
  [99mTc]P1827DS is a potential new inflammation imaging agent, which clearly visualized the abscess in the rabbit E. coli infection model and showed improved biodistribution compared to [99mTc]P483H. However, the infection uptake and biodistribution of [99mTc]P1827DS is not superior to that of [99mTc]HYNIC-IL-8 in this animal model.
authors.affiliation: Bayer Schering Pharma AG, Global Drug Discovery, D-13342 Berlin, Germany. sabine.krause@bayerhealthcare.com
authors.forename: Sabine
authors.initials: S
authors.lastname: Krause
authors.forename: Huub J
authors.initials: HJ
authors.lastname: Rennen
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
authors.forename: Sabine
authors.initials: S
authors.lastname: Baumann
authors.forename: John E
authors.initials: JE
authors.lastname: Cyr
authors.forename: Rajesh
authors.initials: R
authors.lastname: Manchanda
authors.forename: John
authors.initials: J
authors.lastname: Lister-James
authors.forename: Frans C
authors.initials: FC
authors.lastname: Corstens
authors.forename: Ludger M
authors.initials: LM
authors.lastname: Dinkelborg
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D004927:Escherichia coli Infections / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000493:pharmacokinetics*; D016209:Interleukin-8 / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011817:Rabbits; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D006025:Glycosaminoglycans; D016209:Interleukin-8; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C526994:technetium 99m P1827DS; C433789:technetium Tc 99m interleukin 8