High-resolution pH imaging with ratiometric CEST and BIRDS using dual paramagnetic DOTA–tetraglycinate agents

Chemical Exchange Saturation Transfer (CEST) and Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) biosensing methods differ respectively by detecting exchangeable and non-exchangeable protons on the agent. Given that CEST and BIRDS properties observed from the same paramagnetic agent are complimentary, we describe a novel approach for high-resolution pH imaging using dual agents of europium and thulium complexed with DOTA-tetraglycinate. In vitro results test the hypothesis that ratiometric paraCEST attributes are conserved when temperature from paraBIRDS is detected simultaneously, enabling absolute pH imaging. In vivo results in glioblastoma demonstrate feasibility of this dual paraCEST-paraBIRDS biosensing method for high-resolution pH imaging.