Selective irradiation of the vascular endothelium

We developed a unique methodology to selectively irradiate the vascular endothelium in vivo to better understand the role of vascular damage in causing normal tissue radiation side-effects.The relationship between vascular endothelial cell apoptosis and intestinal crypt stem cell death was evaluated using uniform whole-body and selective vascular irradiation techniques. Mice received whole-body epithermal neutron beam irradiation. Additional dose was selectively targeted to endothelial cells from the short-ranged (5-9 [mu]m) particles released from neutron capture reactions in 10B confined to the blood by incorporation into 70-90 nm-diameter liposomes. Mice also received uniform photon doses above and below the threshold for death from the gastrointestinal (GI) syndrome. When plotted versus neutron beam dose, the crypt microcolony assay showed the same dose response for both the neutron beam-only and neutron beam plus boronated liposome groups. The added dose selectively delivered to the microvasculature did not cause any additional crypt loss. Jejunal cross-sections were prepared 4 hrs after irradiation and stained with TUNEL to observe and score apoptotic cells in the villus lamina propria. To uniquely identify the type of cell undergoing apoptosis in the lamina propria, intestinal specimens from various mice in the TUNEL studies were sectioned and stained with Meca-32 to identify endothelial cells and caspase-3 to identify apoptotic cells and visualized using dual-fluorescence microscopy. The TUNEL data showed a low level (~2 apoptotic cells per villus) of apoptosis in the lamina propria for both the uniform (photon or neutron) and selective vascular irradiation conditions that was independent of the administered dose.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Nuclear Science and Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Schuller, Bradley W

Advisor dc:contributor.advisor

• Jeffrey A. Coderre.

• Nuclear Science and Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/44787

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/44787