Hee-Kyung Kim1,
1Department of Medical & Biological
Engineering, Kyungpook National University, Daegu, Korea, Republic of; 2Advanced
Research Institute for Recovery of Human Sensitibiliy, Daegu, Korea, Republic
of; 3Korea Institute of Radiological & Medical Science, Seoul,
Korea, Republic of; 4Bayer Schering Pharma Korea, Seoul, Korea,
Republic of; 5Department of Applied Chemistry, Kyungpook National
University, Daegu, Korea, Republic of; 6Department of Diagnostic
Radiology and Molecular Medicine, Kyungpook National university, Daegu,
Korea, Republic of
We
report the synthesis of 1,1-ferrocendiylamines (L) and their Gd(III)
complexes of the type [Gd(L)(H2O)], referred to as Ferromides, as a new
family of BPCAs. Also reported is the investigation of their thermodynamic
and magnetic resonance properties along with in vitro and in vivo MR studies.
They all exhibit greater thermodynamic stability (ie., logKsel) than their
acyclic and cyclic analogues such as DTPA-BMA, DTPA, and DOTA and compare
favorably to MS-325, a well-known BPCA. The R1 relaxivities of Ferromides are
quite high as compared with other MRI CAs currently in use. In the case of
Ferromide-1, for instance, the R1 relaxivity is 7.5 mM1sec1, which is twice
as high as that of structurally related Dotarem (R1=3.6 mM1sec1). The R1
relaxivity is further increased in an aqueous saline solution of HSA (4.5%
w/v) to be compared quite favorably to that of MS-325, and most strikingly,
the increase is observed even in the absence of the electrostatic
phosphate-HSA interaction. The in vivo MR images of mice obtained with
Ferromide-1 show the contrast enhancement not only in heart and bladder but
also in abdominal aorta, clearly demonstrating the blood-pool effect.