Radiolabeling of Aryl Boronic Ester Derivatives for Cu Catalyzed At-211 Astatination of Biomolecules

Abstract

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