Design, synthesis and characterization of targeted and calcium responsive nano-size contrast agents for magnetic resonance neuroimaging
Başlık çevirisi mevcut değil.
- Tez No: 401575
- Danışmanlar: PROF. DR. MARTIN E. MAIER, PROF. DR. GORAN ANGELOVSKI
- Tez Türü: Doktora
- Konular: Kimya, Chemistry
- Anahtar Kelimeler: Belirtilmemiş.
- Yıl: 2014
- Dil: İngilizce
- Üniversite: Eberhard-Karls-Unıversıtat Tubıngen
- Enstitü: Yurtdışı Enstitü
- Ana Bilim Dalı: Belirtilmemiş.
- Bilim Dalı: Belirtilmemiş.
- Sayfa Sayısı: Belirtilmemiş.
Özet
Özet yok.
Özet (Çeviri)
Magnetic resonance imaging (MRI) is a powerful imaging technique for biomedicine and neuroscience. The contrast agents (CAs) have been developed to help increasing signal intensity for high resolution MR images. Here we report the synthesis of novel multimodal and multivalent CA targeted to the protein (Neutr/strept) avidin and Ca2+ responsive multivalent CAs for MR neuroimaging. In the first project, the avidin-targeted monomeric (MCA-2) and dendrimeric (DCA-2) CAs containing fluorescence label (FITC) and biotin were synthesized and characterized. The relaxometric analysis, avidin binding assay, MRI experiment and fluorescence measurements were performed. G4 PAMAM dendron with 32 surface amino groups was used as a multivalent scaffold. Avidin binding assay showed the binding efficiency of MCA-2 to avidin beads is higher than DCA-2, while the beads bound DCA-2 provided higher MR signal intensity than MCA-2. A number of diverse applications could consequently be envisaged for DCA-2 to investigate living systems. For instance, the polypeptide avidin could be introdruced as a transgene in living cells with techniques of molecular biology for creating model organisms. The second project focused on the synthesis and characterization of the monomeric Ca2+ responsive CA (SCA-1) and dendrimeric Ca2+ responsive CAs (DSCA-1, DSCA-2, and DSCA-3) using G0, G1 or G2 PAMAM dendrimers, which contains 4, 8, and 16 surface amino groups, respectively, as multivalent scaffolds. The relaxometric Ca2+ titrations and in vivo MR experiments in rat brain were performed. In the presence of Ca2+, the longitudinal relaxivity of these SCAs increased. In vivo experiments showed that the DSCAs stayed longer period of time in tissue than SCA-1 providing higher signal intensity. Since the short retention time of the commercial low molecular CAs reduces the quality of MR images, making the diagnosis difficult, the use of DSCAs with a comparably longer retention time may enable development of new imaging protocols with the high quality MR image.
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