Browsing by Subject "prosthetic group"

Tiivistelmä – Referat – Abstract Molecular imaging is visualization, characterization and quantification of biological processes at molecular and cellular levels of living organisms, achieved by molecular imaging probes and techniques such as radiotracer imaging, magnetic resonance imaging and ultrasound imaging. Molecular imaging is an important part of patient care. It allows detection and localization of disease at early stages, and it is also an important tool in drug discovery and development. Positron emission tomography (PET) is a biomedical imaging technique considered as one of the most important advances in biomedical sciences. PET is used for a variety of biomedical applications: i.e. imaging of divergent metabolism, oncology and neurology. PET is based on incorporation of positron emitting radionuclides to drug molecules. As prominent radionuclides used in PET are of short or ultra-short half-lives, the radionuclide is most often incorporated to the precursor in the last step of the synthesis. This has proven to be a challenge with novel targeted radiotracers, as the demand for high specific activity leads to harsh reaction conditions, often with extreme pH and heat which could denature the targeting vector. Click chemistry is a synthetic approach based on modular building blocks. The concept was originally developed for purposes of drug discovery and development. It has been widely utilized in radiopharmaceutical development for conjugating prosthetic groups or functional groups to precursor molecules. Click chemistry reactions are highly selective and fast due to thermodynamic driving force and occur with high kinetics in mild reaction conditions, which makes the concept ideal for development and production of PET radiopharmaceuticals. Isotope exchange (IE) radiosynthesis with trifluoroborate moieties is an alternative labeling strategy for a reasonably high yield 18F labeling of targeted radiopharmaceuticals. As the labeling conditions in IE are milder than in commonly utilized nucleophilic fluorination, the scope of targeting vectors can be extended to labile biomolecules expressing highly specific binding to drug targets, resulting to higher contrast in PET imaging. A trifluoroborate functionalized prosthetic group 3 was synthetized utilizing click chemistry reactions, purified with SPE and characterized with HPLC-MS and NMR (1H , 11B-, 13C-, 19F-NMR). [18F]3 was successfully radiolabeled with RCY of 20.1 %, incorporation yield of 22.3 ± 11.4 % and RCP of >95 %. TCO-functionalized TOC-peptide precursor 6 was synthetized from a commercial octreotide precursor and a commercially available click chemistry building block via oxime bond formation. 6 was characterized with HPLC-MS and purified with semi preparative HPLC. Final product [18F]7 was produced in a two-step radiosynthesis via IEDDA conjugation of [18F]3 and 6. [18F]7 was produced with RCY 1.0 ± 1.0 %, RCP >95 % and estimated molar activity of 0.7 ± 0.8 GBq/µmol. A cell uptake study was conducted with [18F]7 in AR42J cell line. Internalization and specific binding to SSTR2 were observed in vitro.