Studies on 68Ga-Based Agents for PET Imaging of Cancer and Inflammation
Ujula, Tiina (2011-01-14)
Studies on 68Ga-Based Agents for PET Imaging of Cancer and Inflammation
(14.01.2011)
Annales Universitatis Turkuensis D 942 Turun yliopisto
Julkaisun pysyvä osoite on:
https://urn.fi/URN:ISBN:978-951-29-4498-9
https://urn.fi/URN:ISBN:978-951-29-4498-9
Kuvaus
Siirretty Doriasta
Tiivistelmä
Studies on 68Ga-Based Agents for PET Imaging of Cancer and Inflammation
Positron emission tomography (PET) is based on the use of radiolabeled agents and facilitates in vivo imaging of biological processes, such as cancer. Because the detection of cancer is demanding and is often obscured by inflammation, there is a demand for better PET imaging agents.
The aim was to preliminarily evaluate new PET agents for imaging cancer and inflammation using experimental models. 68Ga-chloride and peptides, 68Ga-labeled through 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), targeting matrix metalloproteinase-9 (MMP-9) were tested for tumor imaging. In addition, a 68Ga-DOTA-conjugated peptide targeting vascular adhesion protein-1 (VAP-1), was tested for inflammation imaging. The 68Ga-based imaging agents described here showed potential features by passing the essential in vitro tests, proceeding further to preclinical in vivo evaluation and being able to visualize the target. The target uptake and target-to-background ratios of 68Ga-based agents were, however, not optimal. 68Ga-chloride showed slow clearance caused by its binding to blood transferrin. In the case of 68Ga-DOTA-peptides low in vivo stability and/or low lipophilicity led to too rapid blood clearance and urinary excretion.
The properties of 68Ga-labeled peptides are modifiable, as shown with matrix metalloproteinase-9 targeting ligands. In the conclusion of this PhD thesis, 68Ga-based agents for PET imaging of cancer and inflammation could be applied in the development of drugs, earlier diagnostics and following-up of the efficacy of therapies.
Positron emission tomography (PET) is based on the use of radiolabeled agents and facilitates in vivo imaging of biological processes, such as cancer. Because the detection of cancer is demanding and is often obscured by inflammation, there is a demand for better PET imaging agents.
The aim was to preliminarily evaluate new PET agents for imaging cancer and inflammation using experimental models. 68Ga-chloride and peptides, 68Ga-labeled through 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), targeting matrix metalloproteinase-9 (MMP-9) were tested for tumor imaging. In addition, a 68Ga-DOTA-conjugated peptide targeting vascular adhesion protein-1 (VAP-1), was tested for inflammation imaging. The 68Ga-based imaging agents described here showed potential features by passing the essential in vitro tests, proceeding further to preclinical in vivo evaluation and being able to visualize the target. The target uptake and target-to-background ratios of 68Ga-based agents were, however, not optimal. 68Ga-chloride showed slow clearance caused by its binding to blood transferrin. In the case of 68Ga-DOTA-peptides low in vivo stability and/or low lipophilicity led to too rapid blood clearance and urinary excretion.
The properties of 68Ga-labeled peptides are modifiable, as shown with matrix metalloproteinase-9 targeting ligands. In the conclusion of this PhD thesis, 68Ga-based agents for PET imaging of cancer and inflammation could be applied in the development of drugs, earlier diagnostics and following-up of the efficacy of therapies.
Kokoelmat
- Väitöskirjat [2845]