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REPORT

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Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Interaction of Ultrasound with Tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Heat Generation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Cavitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Radiation Force . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Nanoparticles for Ultrasound-mediated Gene Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Microbubbles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Micelles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Liposomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Biological Carriers: Viruses, Stem Cells and Immune Cells . . . . . . . . . . . . . . . . . . . 4 Image-based Analysis of Pharmacodistribution and Pharmacokinetics . . . . . . . . . . . . . . . . 4.1 Pharmacokinetics with MR Contrast Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Labelling with MR Contrast Agents to Allow Tracking . . . . . . . . . . . . . . . . . . . . . . . 5 Gene Therapy: Ultrasound-guided Gene Delivery and Gene Expression . . . . . . . . . . . . . . 5.1 Ultrasound Exposure and Transfection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2 Gene Expression Control with MR-guided Focused Ultrasound and Temperature-sensitive Promoters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Abstract The interaction of ultrasound with tissue leads to radiation pressure, heat generation, and cavitation. These phenomena have been utilised for local gene delivery, transfection and control of expression. Specially designed nanocarriers or adapted ultrasound contrast agents can further enhance local delivery by: (1) increased permeability of cell membranes; (2) local release of genes. Biological carriers may also be used for local gene delivery. Stem cells and immune cells appear especially promising because of their homing capabilities to lesion sites. Imaging methods can be employed for pharmacodistribution and pharmacokinetics. MRI contrast agents can serve as non-invasive reporters on gene distribution Chrit

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