Targeted delivery of antibodies through the blood-brain barrier by MRI-guided focused ultrasound.
The blood-brain barrier (BBB) is a persistent obstacle for the local delivery of macromolecular therapeutic agents to the central nervous system (CNS). Many drugs that show potential for treating CNS diseases cannot cross the BBB and there is a need for a non-invasive targeted drug delivery method that allows local therapy of the CNS using larger molecules. We developed a non-invasive technique that allows the image-guided delivery of antibody across the BBB into the murine CNS. Here, we demonstrate that subsequent to MRI-targeted focused ultrasound induced disruption of BBB, intravenously administered dopamine D(4) receptor-targeting antibody crossed the BBB and recognized its antigens. Using MRI, we were able to monitor the extent of BBB disruption. This novel technology should be useful in delivering macromolecular therapeutic or diagnostic agents to the CNS for the treatment of various CNS disorders.
Kinoshita
Manabu
M
Department of Radiology, Brigham and Womens Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
McDannold
Nathan
N
Jolesz
Ferenc A
FA
Hynynen
Kullervo
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000528:radiation effects; D016503:Drug Delivery Systems / Q000379:methods*; D007167:Immunotherapy / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D050638:Receptors, Dopamine D4 / Q000276:immunology; D013010:Sonication
D000911:Antibodies, Monoclonal; D050638:Receptors, Dopamine D4