| Publication Type |
dissertation |
| School or College |
College of Pharmacy |
| Department |
Pharmaceutics & Pharmaceutical Chemistry |
| Author |
Mohs, Aaron Michael |
| Title |
Biodegradable macromolecular contrast agents for magnetic resonance imaging |
| Date |
2006-12 |
| Description |
Magnetic resonance imaging (MRI) is a powerful tool for diagnostic imaging. Low molecular weight paramagnetic Gd(III) complexes are often used to enhance the depiction of disease morphology or functionality. Although safe, these complexes have poor pharmacokinetic performance limiting their application when selective enhancement of the blood pool is needed. Macromolecular Gd(III) complexes have demonstrated significantly higher contrast enhancement of the vasculature because their large size limits their clearance and diffusion from the blood pool into surrounding tissue. Macromolecular Gd(III) complexes have shown superior efficacy over clinically approved contrast agents in the noninvasive detection of a wide range of disease in preclinical studies. Unfortunately, the prolonged circulation of previously designed macromolecular Gd(III) complexes results in the metabolic release and subsequent tissue uptake of highly toxic Gd(III) ions. A promising alternative to this challenge is the development of biodegradable polydisulfide Gd(III) complexes. Initially, these polymers would circulate in the vasculature giving the efficacy of a macromolecular contrast agent, but over time would be gradually degraded via the thiol-disulfide exchange reaction yielding small Gd(III) complexes that can readily be cleared. Specifically, the work undertaken in this project was to modify the degradation of polydisulfide Gd(III) complexes by conjugating poly(ethylene glycol) (PEG) around the disulfide bond of poly(GdDTPA-co-L-cystine) (GDCP) yielding PEG-GDCP. PEG-GDCP was synthesized in a variety of molecular weights, PEG grafting degrees, and PEG sizes. In vitro, these agents showed degradation to a thiol, which was dependent on the type of PEG grafting. In vivo, PEG-GDCP showed excellent enhancement of the blood pool of mice compared to a clinical control, Gd(DTPA-BMA), including very small vasculature. One agent tested, PEG<sub>1000 |
| Type |
Text |
| Publisher |
University of Utah |
| Subject |
Imaging Enhancement |
| Subject MESH |
Magnetic Resonance Imaging |
| Dissertation Institution |
University of Utah |
| Dissertation Name |
PhD |
| Language |
eng |
| Relation is Version of |
Digital reproduction of "Biodegradable macromolecular contrast agents for magnetic resonance imaging Spencer S. Eccles Health Sciences Library. |
| Rights Management |
© Aaron Michael Mohs. |
| Format Medium |
application/pdf |
| Format Extent |
3,600,476 bytes |
| Identifier |
undthes,3924 |
| Source |
Original University of Utah Spencer S. Eccles Health Sciences Library (no longer available) |
| Funding/Fellowship |
NIH grants R01 EB00489 and R33 CA095873; PhRMA Foundation predoctoral fellowship |
| Master File Extent |
3,600,503 bytes |
| ARK |
ark:/87278/s6sj1ncb |
| Setname |
ir_etd |
| ID |
190623 |
| Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6sj1ncb |
