Development of Ln(III) Derivatives as 19 F Parashift Probes.

19 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 LnL 19 F parashift probes. We evaluated trans-gadolinium paramagnetic lanthanides compared to diamagnetic YL for 19 F chemical shift and relaxation rate enhancement. The paramagnetic contribution to chemical shift (δ PCS ) for paramagnetic LnL exhibited either shifts to lower frequency (δ PCS < 0 for TbL , DyL , and HoL ) or shifts to higher frequency (δ PCS > 0 for ErL , TmL , and YbL ) compared to YL 19 F spectroscopic signal. Zero-echo time pulse sequences achieved 56-fold sensitivity enhancement for DyL over YL , while developing probe-specific pulse sequences with fast delay times and acquisition times achieved 0.6-fold enhancement in limit of detection for DyL . DyL provides an attractive platform to develop 19 F parashift probes for ratiometric detection of enzymatic activity.