Biochemical and Biophysical Research Communications
Targeted delivery of antibodies through the blood–brain barrier by MRI-guided focused ultrasound
Section snippets
Methods
Antibody. The antibody used in this experiment is a rabbit anti-human dopamine D4 receptor antibody, which recognizes the 3rd extracellular domain (Ac-176-185) of the human dopamine D4 receptor (Cat# 324405, Merck KGaA, Darmstadt, Germany) [20]. Cross-reactivity of this antibody for mouse brain was confirmed by standard immunohistochemistry with a dilution of 1:10,000.
Ultrasound equipment. The ultrasound fields were generated by an in-house manufactured, focused, piezoelectric transducer with a
Results
Using a mouse model and MRI-guided focused ultrasound-induced BBB disruption, we made an attempt to deliver a polyclonal antibody against the extracellular domain of the dopamine D4 receptor to the CNS. The antibody is originated from rabbit IgG. Therefore, the rabbit polyclonal antibody should be able to be detected with an anti-rabbit IgG antibody on the sections with successful BBB disruption. The experiment setup is illustrated in Fig. 1A, which is a setup similar to those of our previous
Discussion
Today many molecular targeting drugs have been developed for various diseases, such as anti-HER2 monoclonal antibody; herceptin for breast cancer [23], and anti-CD20 monoclonal antibody; Rituximab for malignant lymphoma [24]. There are also evidences suggesting that antibodies against the Aβ can reverse cognitive deficits in early Alzheimer’s disease [25], [26]. However, for in vivo clinical treatment, these promising large molecular agents are not applicable because of the presence of BBB.
Acknowledgments
This investigation was supported by the Shinya International Exchange Fund, the Osaka Medical Research Foundation for Incurable Diseases, the Osaka Neurological Institute, NIH Grant (EB003268) and U41-RR 019703 NIH P01CA67165-03.
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