Details

Autor(en) / Beteiligte

• Saab-Ismail, Nada H
• Simor, Tamás
• Gaszner, Balázs
• Lóránd, Tamás
• Szöllösy, Márta
• Elgavish, Gabriel A

Titel

Synthesis and in Vivo Evaluation of New Contrast Agents for Cardiac MRI

Ist Teil von

• Journal of medicinal chemistry, 1999-07, Vol.42 (15), p.2852-2861

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

1999

Quelle

MEDLINE

Beschreibungen/Notizen

• Analogues 2 − 6 of N 3,N 6-bis(2‘-myristoyloxyethyl)-1,8-dioxotriethylenetetraamine-N,N,N‘,N‘-tetraacetic acid (BME-DTTA) (1), which like 1 are also based on the DTTA structure but contain shorter fatty acyl chains, were synthesized to improve the water solubility of the corresponding gadolinium complexes. The gadolinium complexes of 1 and 3−5 have very low solubility in water. Thus liposomal preparations are necessary for their in vivo MRI application. These liposomal preparations retain high in vitro relaxivities (27.1, 21.57, 20.32, 23.1 s-1 mM-1, respectively) and induce sustained MRI signal intensity enhancements (67.2, 38.4, 52.1, 41.7 in arbitrary units, respectively). The gadolinium complex of 2 is quite soluble in water. Its lifetime in the blood stream, however, is short. The gadolinium complex of analogue 6, N-(2-butyryloxyethyl)-N‘-(2-ethyloxyethyl)-N,N‘-bis[N‘ ‘,N‘ ‘-bis(carboxymethyl)acetamido]-1,2-ethanediamine (ABE-DTTA), has demonstrated its potential as a water-soluble, cardiac-specific, MRI contrast agent. It is completely soluble in water at a 25 mM concentration, allowing the preparation of an injectable dose. The in vitro relaxivity of the complex is 16.24 s-1 mM-1. The agent shows a specific accumulation in the heart tissue reaching its maximum within 15 min after administration, inducing a sustained MRI signal intensity enhancement of 43.6%. This enhancement lasts for at least 3 h, thus indicating a reasonably long lifetime of this contrast agent in the myocardium without deleterious effects on heart function parameters.