title: Targeted delivery of antibody-based therapeutic and imaging agents to CNS tumors: crossing the blood-brain barrier divide.
abstract: BACKGROUND
  Brain tumors are inherently difficult to treat in large part due to the cellular blood-brain barriers (BBBs) that limit the delivery of therapeutics to the tumor tissue from the systemic circulation. Virtually no large molecules, including antibody-based proteins, can penetrate the BBB. With antibodies fast becoming attractive ligands for highly specific molecular targeting to tumor antigens, a variety of methods are being investigated to enhance the access of these agents to intracranial tumors for imaging or therapeutic applications.
  
  
  METHODS
  This review describes the characteristics of the BBB and the vasculature in brain tumors, described as the blood-brain tumor barrier (BBTB). Antibodies targeted to molecular markers of central nervous system (CNS) tumors will be highlighted, and current strategies for enhancing the delivery of antibodies across these cellular barriers into the brain parenchyma to the tumor will be discussed. Noninvasive imaging approaches to assess BBB/BBTB permeability and/or antibody targeting will be presented as a means of guiding the optimal delivery of targeted agents to brain tumors.
  
  
  CONCLUSIONS
  Preclinical and clinical studies highlight the potential of several approaches in increasing brain tumor delivery across the BBB divide. However, each carries its own risks and challenges. There is tremendous potential in using neuroimaging strategies to assist in understanding and defining the challenges to translating and optimizing molecularly targeted antibody delivery to CNS tumors to improve clinical outcomes.
authors.affiliation: University of Pennsylvania, Perelman School of Medicine, Nuclear Medicine & Clinical Molecular Imaging, Department of Radiology, 231 S. 34 Street, Room 288, Philadelphia, PA 19104, USA achacko@upenn.edu
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Chacko
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Li
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Pryma
authors.forename: Steven
authors.initials: S
authors.lastname: Brem
authors.forename: George
authors.initials: G
authors.lastname: Coukos
authors.forename: Vladimir
authors.initials: V
authors.lastname: Muzykantov
mesh_terms: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000098:blood supply; D001932:Brain Neoplasms / Q000098:blood supply* / Q000628:therapy*; D002199:Capillary Permeability; D016503:Drug Delivery Systems; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D059906:Neuroimaging / Q000379:methods; D004364:Pharmaceutical Preparations / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000922:Immunotoxins; D004364:Pharmaceutical Preparations