Annexin A5-Conjugated Polymeric Micelles For Dual Spect and Optical Detection of Apoptosis

<p>Apoptosis, a form of programmed cell death, is critical to homoeostasis, normal development, and physiology. Dysregulation of apoptosis can lead to the accumulation of unwanted cells, such as occurs in cancer, and the removal of needed cells or disorders of normal tissues, such as heart, neurodegenerative, and autoimmune diseases. Noninvasive detection of apoptosis may play an important role in the evaluation of disease states and response to therapeutic intervention for a variety of diseases. It is desirable to have an imaging method to accurately detect and monitor this process in patients. In this study, we developed annexin A5-conjugated polymeric micellar nanoparticles dual-labeled with a near-infrared fluorescence fluorophores (Cy7) and a radioisotope (¹¹¹In), named as ¹¹¹In-labeled annexin A5-CCPM. <em>In vitro</em> studies demonstrated that annexin A5-CCPM could strongly and specifically bind to apoptotic cells. <em>In vivo</em> studies showed that apoptotic tissues could be clearly visualized by both single photon emission computed tomography (SPECT) and fluorescence molecular tomography (FMT) after intravenous injection of ¹¹¹In-labeled Annexin A5-CCPM in 6 different apoptosis models. In contrast, there was little signal in respective healthy tissues. All the biodistribution data confirmed imaging results. Moreover, histological analysis revealed that radioactivity count correlated with fluorescence signal from the nanoparticles, and both signals co-localized with the region of apoptosis. In sum, ¹¹¹In-labeled annexin A5-CCPM allowed visualization of apoptosis by both nuclear and optical imaging techniques. The complementary information acquired with multiple imaging techniques should be advantageous in improving diagnostics and management of patients.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2011

Author dc:creator

• Zhang, Rui

Contributors dc:contributor

• Chun Li
• Diana Chow
• Zhen Fan

• Apoptosis
• Annexin A5
• Polymeric Micelles
• Nuclear Imaging
• Fluorescence Optical Imaging
• Other Analytical, Diagnostic and Therapeutic Techniques and Equipment

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/184

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1217