A carregar...
Publicação
Multifunctional organometallic compounds for Auger therapy
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 3.67 MB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
Abstract Auger emitters gained significant interest in the past years due to the favorable suitability for target therapy at cellular level.Among Auger emitters, 99mTc seems like the most appealing candidate for this task due to its great advantages regarding low cost, high availability and almost ideal radiochemical properties. The short range of Auger electrons demands that the radionuclide must be as close as possible to the target, usually the nuclear DNA, in order to cause significant therapeutic effects. Thus, the search for efficient delivery systems is the major challenge for Auger therapeutic applications. Radioactive complexes capable of entering the cell andtarget the nucleus showing affinity for the DNA molecule have been reported in the literature. Such compounds comprise efficient multifunctional chelatorswith the ability to stabilize the fac-[99mTc(CO)3]+core, as well as DNA-intercalating agents that ensure close proximity to the target. Herein we aimed to synthesize 99mTc complexes (Tc1-4) stabilizedby multifunctional chelators of the pyrazole-diaminetype, containing anthracene (L1and L2) or acridine orange (L3and L4) as DNA-binding groups with longer (L2and L3) or shorter (L1and L4) spacer between the latter and the chelating agent. The corresponding Re complexes (Re1-4) were also foreseen for full chemical characterization. Due to the demanding synthesis processes and available time, only Tc1and Tc2could be synthesized, characterized and biologically evaluated. The Re congeners showed ability to interact with the CT-DNA molecule trough spectroscopic studies. Tc1and Tc2also showed great ability to target the nucleus, once diffused into the cells of B16-F1 murine melanoma and PC3 human prostate cells, but no radio-cytotoxic effect in these cell lines. Although efficient delivery system at subcellular level could be provided in this work, the relevance of the complexes for the design of Auger emitting 99mTc radiopharmaceuticals could not be demonstrated.
Descrição
Palavras-chave
Nuclear medicine Radiotherapy Radiometal Auger electrons Technetium-99m DNA-interaction