Development of Ln(III) Derivatives as F Parashift Probes.

F parashift probes with paramagnetically shifted reporter nuclei provide attractive platforms to develop molecular imaging probes. These probes enable ratiometric detection of molecular disease markers using a direct detection technique. Here, we describe a series of trivalent lanthanide (Ln(III)) complexes that are structural analogues of the clinically approved MR contrast agent (CA) ProHance to obtain F parashift probes. We evaluated trans-gadolinium paramagnetic lanthanides compared to diamagnetic for F chemical shift and relaxation rate enhancement. The paramagnetic contribution to chemical shift (δ) for paramagnetic exhibited either shifts to lower frequency (δ < 0 for , , and ) or shifts to higher frequency (δ > 0 for , , and ) compared to F spectroscopic signal. Zero-echo time pulse sequences achieved 56-fold sensitivity enhancement for over , while developing probe-specific pulse sequences with fast delay times and acquisition times achieved 0.6-fold enhancement in limit of detection for . provides an attractive platform to develop F parashift probes for ratiometric detection of enzymatic activity.