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Abstract #3861

Transition metal based phosphonated macrocyclics for pH biosensing

Sandeep Kumar Mishra1, Sara Kurdi2, Daniel Coman2, and Fahmeed Hyder2
1Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States, 2Department of Biomedical Engineering, Yale University, New Haven, CT, United States

Synopsis

Keywords: Contrast Agents, Contrast Agents, MRI; MRSI; pH; Temperature; Biosensors; Transition metals

Motivation: Lanthanide ion-based first-generation MRI contrast agents (like GBCAs) enhance detection of pathologic structures by shortening water proton relaxation but provide no physiological information.

Goal(s): Develop second-generation MRI agents that enhance relaxivity-based detection and selectively map physiological parameters through hyperfine shifted proton resonances.

Approach: Designing and synthesizing novel paramagnetic MR agents with Co(II) and Ni(II) ions coordinated phosphonated macrocyclic ligands for pH biosensing, aiding early detection of tumors, ensuring clinical translation.

Results: We synthesized Co(II) and Ni(II) coordinated phosphonated macrocyclic complexes [M(II)L]. Co(II)Lx- has 6.5 ppm/pH sensitivity, 1.5-fold larger than TmDOTP5-, while Ni(II)Lx- has 2.7 ppm/pH, comparable to TmDOTP5-.

Impact: The Co(II)Lx- exhibited highest pH sensitivity among all reported biosensors. These biocompatible pH sensors are under evaluation for in vivo pH mapping, aiming to enable early cancer diagnosis and holding strong potential for clinical translation.

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