The current thesis work concerns the study of the formation of Ag+, Cu2+ and Cu+ complexes with the chelating agent 1,4,7-tris[2-(methylsulfanil)ethyl]-1,4,7-triazacyclononane, with potential use as radiopharmaceuticals. Silver-111 is a nuclide of interest for nuclear medicine. It has a β− decay with the emission of medium-energy particles (E = 360 keV) and a fairly long half-life (7.47 days), characteristics that make it a good candidate for radioimmunotherapy. Furthermore, it could be used in the SPECT diagnosis, thanks to the low energy γ emission (Eγ = 245.4 and 342.1 keV). Also, silver-111 is a theranostic agent in combination with silver-103 and silver-104, isotopes suitable for PET as they are β+ emitters. Another possible theranostic couple is represented by copper-64 and copper-67. The first radionuclide, thanks to the co-emission of β+ and β− particles, can potentially be used in nuclear medicine both for diagnostic purposes, through PET, and for therapeutic purposes. The second radionuclide is a β− and γ rays emitter and so it could be used in diagnostics (SPECT) and in therapy. In order to use a radiometal in nuclear medicine, it is necessary to devise a radiopharmaceutical that contains it and directs it to the site of interest, avoiding the release of radioactivity in unwanted areas. Metal-based radiopharmaceuticals generally consist of the radionuclide of interest, a carrier biomolecule that allows binding to target receptors, a bifunctional chelator that provides the metal complex with thermodynamic stability and kinetic inertia under physiological conditions, and a linker that unites the complex to the biomolecule and which allows to modulate the properties of the radiopharmaceutical. This thesis work focalized on the chelator part of the radiopharmaceutical, and on its interactions with the metal ions of interest, and 1,4,7-tris[2-(methylsulfanyl) ethyl]-1,4,7-triazacyclonane was considered as possible chelator. The formation of Ag+, Cu2+ and Cu+ complexes with this chelator in aqueous solution has been investigated using potentiometric, voltammetric, NMR spectroscopic and UV-vis spectrophotometric, in order to determine their thermodynamic and kinetic properties. The analyzed chelator and its complexes with Ag+, Cu2+ and Cu+ were compared with systems previously studied, with the aim to evaluate the considered chelator as possible radiopharmaceutical component.
Il presente lavoro di tesi riguarda lo studio della formazione dei complessi di Ag+, Cu2+ e Cu+ con il chelante 1,4,7-tris[2-(metilsulfanil)etil]-1,4,7-triazaciclononano, con potenzialità di impiego come radiofarmaci. L’argento-111 è un nuclide d’interesse per la medicina nucleare in quanto presenta un decadimento β− con emissione di particelle a media energia (E = 360 keV) e un tempo di emivita abbastanza lungo (7.47 giorni), caratteristiche che lo rendono un valido candidato per la radioimmunoterapia. Inoltre, potrebbe essere usato sia nella diagnosi mediante SPECT, grazie all’emissione γ a bassa energia (Eγ = 245.4 e 342.1 keV), sia come agente teranostico in combinazione con argento-103 e argento-104, isotopi adatti alla PET in quanto emettitori β+. Oltre all’argento-111, anche il rame-64 e il rame-67 rappresentano una possibile coppia teranostica. Il primo radionuclide, grazie alla co-emissione di particelle β+ e β− può essere potenzialmente utilizzato in medicina nucleare sia per scopi diagnostici, tramite PET, che terapeutici; il secondo, invece, essendo un emettitore β− e di raggi γ, potrebbe essere impiegato nell’imaging mediante SPECT e nella terapia. Per poter utilizzare un radiometallo in medicina nucleare, è necessario ideare un radiofarmaco che lo contenga e lo direzioni nel sito d’interesse evitandone il rilascio in zone non desiderate. I radiofarmaci metal-based sono generalmente costituiti dal radionuclide di interesse, da una biomolecola carrier che consente il legame con i recettori target, da un chelante bifunzionale che fornisce al complesso metallico stabilità termodinamica e inerzia cinetica in condizioni fisiologiche, e da un linker che unisce il complesso alla biomolecola e che consente di modulare le proprietà dell’intero radiofarmaco. In questo lavoro di tesi ci si è focalizzati sulla parte del chelante e sulle sue interazioni con gli ioni metallici di interesse, e si è considerato come possibile chelante il 1,4,7-tris[2-(metilsulfanil)etil]-1,4,7-triazaciclononano. La formazione dei complessi di tale chelante con Ag+, Cu2+ e Cu+ in soluzione acquosa è stata indagata mediante l’uso di tecniche potenziometriche, spettroscopiche NMR, spettrofotometriche UV-vis e voltammetriche, al fine di determinarne le proprietà termodinamiche e cinetiche. Tali proprietà sono state poi confrontate con quelle di sistemi simili studiati in precedenza, per permettere di valutare le potenzialità del chelante considerato in ambito radiofarmaceutico.
STUDIO DELLA FORMAZIONE DI COMPLESSI DI 1,4,7-TRIS[2-(METILSULFANIL)ETIL]-1,4,7-TRIAZACICLONONANO CON Ag(I), Cu(II) E Cu(I)
DEL VECCHIO, ALESSANDRO
2021/2022
Abstract
The current thesis work concerns the study of the formation of Ag+, Cu2+ and Cu+ complexes with the chelating agent 1,4,7-tris[2-(methylsulfanil)ethyl]-1,4,7-triazacyclononane, with potential use as radiopharmaceuticals. Silver-111 is a nuclide of interest for nuclear medicine. It has a β− decay with the emission of medium-energy particles (E = 360 keV) and a fairly long half-life (7.47 days), characteristics that make it a good candidate for radioimmunotherapy. Furthermore, it could be used in the SPECT diagnosis, thanks to the low energy γ emission (Eγ = 245.4 and 342.1 keV). Also, silver-111 is a theranostic agent in combination with silver-103 and silver-104, isotopes suitable for PET as they are β+ emitters. Another possible theranostic couple is represented by copper-64 and copper-67. The first radionuclide, thanks to the co-emission of β+ and β− particles, can potentially be used in nuclear medicine both for diagnostic purposes, through PET, and for therapeutic purposes. The second radionuclide is a β− and γ rays emitter and so it could be used in diagnostics (SPECT) and in therapy. In order to use a radiometal in nuclear medicine, it is necessary to devise a radiopharmaceutical that contains it and directs it to the site of interest, avoiding the release of radioactivity in unwanted areas. Metal-based radiopharmaceuticals generally consist of the radionuclide of interest, a carrier biomolecule that allows binding to target receptors, a bifunctional chelator that provides the metal complex with thermodynamic stability and kinetic inertia under physiological conditions, and a linker that unites the complex to the biomolecule and which allows to modulate the properties of the radiopharmaceutical. This thesis work focalized on the chelator part of the radiopharmaceutical, and on its interactions with the metal ions of interest, and 1,4,7-tris[2-(methylsulfanyl) ethyl]-1,4,7-triazacyclonane was considered as possible chelator. The formation of Ag+, Cu2+ and Cu+ complexes with this chelator in aqueous solution has been investigated using potentiometric, voltammetric, NMR spectroscopic and UV-vis spectrophotometric, in order to determine their thermodynamic and kinetic properties. The analyzed chelator and its complexes with Ag+, Cu2+ and Cu+ were compared with systems previously studied, with the aim to evaluate the considered chelator as possible radiopharmaceutical component.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/30684