Abstract
(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.