Five amphiphilic, anionic Mn(II) complexes were synthesized
as
contrast agents targeted to organic anion transporting polypeptide
transporters (OATP) for liver magnetic resonance imaging (MRI). The
Mn(II) complexes are synthesized in three steps, each from the commercially
available trans-1,2-diaminocyclohexane-N,N,N′,N′-tetraacetic acid (CDTA) chelator, with T
1-relaxivity of complexes ranging between 2.3 and 3.0
mM–1 s–1 in phosphate buffered
saline at an applied field strength of 3.0 T. Pharmacokinetics were
assessed in female BALB/c mice by acquiring T
1-weighted images dynamically for 70 min after agent administration
and determining contrast enhancement and washout in various organs.
Uptake of Mn(II) complexes in human OATPs was investigated through
in vitro assays using MDA-MB-231 cells engineered to express either
OATP1B1 or OATP1B3 isoforms. Our study introduces a new class of Mn-based
OATP-targeted contrast that can be broadly tuned via simple synthetic
protocols.