Radiolabeling of Aryl Boronic Ester Derivatives for Cu Catalyzed At-211 Astatination of Biomolecules
Typ
Examensarbete för masterexamen
Program
Materials chemistry (MPMCN), MSc
Publicerad
2020
Författare
Linsten, Emma
Modellbyggare
Tidskriftstitel
ISSN
Volymtitel
Utgivare
Sammanfattning
Targeted alpha therapy is an area of research for treatment of spread microscopic cancer. Among theradioactivenuclidesthatemitalpha-radiationandareeligibleforuseintargetedalphatherapy, the astatine isotope 211At has been seen as a promising candidate. A common method of attaching the astatine to a targeting biomolecule has used a type of alkyltin reagent as a linking molecule. Since alkyltins are very toxic their use is not preferred. In 2016, an alternative copper catalyzed methodusinganarylboronicacidderivativeasalinkingmoleculewaspresented. In2018,thesame methodwasappliedonarylboronicesterderivativesaswell. Inthesepreviousstudiesofthecopper catalyzedmethod,theradioactivenuclidewasattachedtothelinkingmoleculewhichcouldthenbe conjugated to a targeting biomolecule. In order to minimize radiation dose, the preferred method of attachment would be to conjugate the linking molecule to a targeting biomolecule first and then attachtheradioactivenuclide. Thepossibilityofusingthecoppercatalyzedmethodforattachment toanalreadyconjugatedbiomoleculewasinvestigatedbyexaminingreactionconditionswhichcould make a transition from a reaction in organic solution to a reaction in aqueous solution possible. As a reaction in aqueous solution proved possible with good yields, the reaction was investigated for attachingthenuclidetoaconjugatedbiomolecule. Afteroptimizingthereactionconditions,ayield of 57.8% was achieved which indicated that the copper catalyzed method could be used to attach a radionuclidetoaconjugatedbiomolecule. Byfurtheroptimizingthereaction,itseemsplausiblethat thecoppercatalyzedmethodcanreplacethealkyltinrequiringmethod
Beskrivning
Ämne/nyckelord
Iodination , astatination , radiopharmaceuticals , targeted alpha therapy , arylboronicester derivative