title: Central delivery of iodine-125-labeled cetuximab, etanercept and anakinra after perispinal injection in rats: possible implications for treating Alzheimer's disease.
abstract: BACKGROUND
  Alzheimer's disease is a debilitating condition, and the search for an effective treatment is ongoing. Inflammation, in reaction to amyloid deposition, is thought to accelerate cognitive decline. With tumor necrosis factor α being an important proinflammatory cytokine, a recent trial investigated the effect of the tumor necrosis factor α inhibitor etanercept after peripheral administration in patients with Alzheimer's disease. Although there was no significant effect, others have claimed spectacular effects of etanercept after perispinal injection. In the present study, the central delivery of drugs with a large molecular weight was evaluated after injection in the cervical perispinal region in rats. If successful, this strategy might increase therapeutic options for patients with Alzheimer's disease.
  
  
  METHODS
  Nine male Sprague-Dawley rats were given injections of iodine-125-labeled cetuximab (146 kDa), etanercept (51 kDa), and anakinra (17 kDa). Each radioiodinated drug was injected in the perispinal region in two rats and into the dorsal tail vein in one rat. Directly after injection, the rats were placed in a head-down position for 3 minutes to direct blood flow into the valveless vertebral venous system. A single-positron emission computed tomography scan was acquired starting 5 minutes after injection, subsequently the rats were euthanized and bio-distribution was determined.
  
  
  RESULTS
  Intracranial delivery of the radiolabeled drugs could not be visualized in all but one of the rats. Injected drugs accumulated locally in the perispinal region.
  
  
  CONCLUSIONS
  In this study, no evidence could be found for the delivery of drugs to the central nervous system after perispinal injection. Additional research is needed before this treatment can be used in patients with Alzheimer's disease.
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. megan.roerink@radboudumc.nl.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Roerink
authors.affiliation: Department of Neurosurgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. r.j.m.groen@umcg.nl.
authors.forename: Rob Jm
authors.initials: RJ
authors.lastname: Groen
authors.affiliation: Department Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. gerben.franssen@radboudumc.nl.
authors.forename: Gerben
authors.initials: G
authors.lastname: Franssen
authors.affiliation: Central Animal Facility Nijmegen, Radboud University Medical Center, Nijmegen, The Netherlands. bianca.lemmers-vandeweem@radboudumc.nl.
authors.forename: Bianca
authors.initials: B
authors.lastname: Lemmers-van de Weem
authors.affiliation: Department Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. otto.boerman@radboudumc.nl.
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. jos.vandermeer@radboudumc.nl.
authors.forename: Jos Wm
authors.initials: JW
authors.lastname: van der Meer
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D002491:Central Nervous System Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000068818:Cetuximab / Q000008:administration & dosage*; D000068800:Etanercept / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D007278:Injections, Spinal; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes; D008297:Male; D011187:Posture; D019275:Radiopharmaceuticals; D017207:Rats, Sprague-Dawley; D013623:Tail / Q000098:blood supply; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D002491:Central Nervous System Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D000068800:Etanercept; D000068818:Cetuximab