Page 171 - Cellular Imaging in Regenerative Medicine, Cancer and Osteoarthritis

Summary, Discussion, Concluding remarks
due to sequential compression and expansion caused by pressure variations. Cell membrane permeability is increased this way, because the microbubbles cause shear stress on the cell membrane. They create transient, non-lethal holes in the plasma membrane, through which a drug/gene/label is able to diffuse into the cell (27-29). Acoustical pressure, sonication time, and SPIO incubation time play a role in safe and optimal endothelial cell labelling. The next step following the in vitro experiments should be in vivo experiments for real time targeted microbubble sonoporation. These can, for example, be performed with chicken embryos. Their chorioallantoic membrane (CAM) is a simple, highly vascularized extraembryonic membrane and is used to study angiogenesis and vascular biology (30). The CAM has great accessibility and is easy to handle for both intervention and imaging of the vasculature. SPIO labelling of the cells of the vessel wall can be monitored with a high speed camera. The microbubble behavior can be recorded and the cellular and tissue response might allow a better understanding of microbubble-drug-cell interaction.
Cancer cell imaging for diagnosis and therapy
Targeting of overexpressed receptors on the cell membrane of certain cells is applied in peptide radionuclide receptor therapy (PRRT) and imaging. A radioactive tracer is composed to target the receptor upon injection in the bloodstream, which can be visualised with a PET or SPECT scan. Availability of a tracer to target cells can be compromised for example by presence of enzymes that degrade the tracer. Too fast excretion of the tracer from blood is also problematic, because the time window for the tracer to reach the cell of interest is very short.
In Chapter 5 we describe our research aiming to increase in vivo stability of an Indium-111 labelled radiopeptide targeting the gastrin-releasing peptide receptor (GRPR). This is a G-protein coupled receptor expressed at high density in a number of cancer types such as prostate cancer, breast cancer, and gastrointestinal cancer, which makes it an attractive target for peptide radionuclide receptor therapy (31, 32). Multiple GRPR radioligands have been synthesized during the past decade, mainly for the purpose of receptor- mediated nuclear imaging and therapy (33, 34). Our GRPR antagonist, Sarabesin-3, labelled with the positron-emitting radionuclide Gallium-68
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