FATTY-ACYL IMINOPOLYCARBOXYLATES - LIPOPHILIC BIFUNCTIONAL CONTRAST AGENTS FOR NMR IMAGING

New fatty‐acyl contrast agents, N3−2′‐myristoyloxyethyl‐ N6−2′‐hydroxyethyl‐1, 8‐dioxotriethylenetetraamine‐N, N, N′, N′ ‐tetraacetic acid (MHE‐DTTA) and N3, N6‐bis (2′‐myristoyloxyethyl)‐1, 8‐dioxo‐triethylenetetraamine‐N, N, N′, N′‐tetraacetic acid (BME‐DTTA) were prepared by sequential alkylation, acylation, and catalytic hydrogenation from bis(hydroxyethyl)‐ethylenediamine with satisfactory yields (overall 36–46%). The 1:1 gadolinium complexes of the ligands MHE‐DTTA and BME‐DTTA were incorporated into liposomes and their relaxivities in vitro were determined. The relaxivities of both agents were similar and were greater than those of Gd3+ aquoion, Gd(EDTA), and Gd(DTPA) at both 0.23 T and 0.47 T. The relaxivities of these two agents increased from the lower to the higher magnetic field, indicating a positive field dependence. This is advantageous because of the widespread use of high‐field (B0 > 0.5 T) NMR imaging instruments. Stability constants (log K) of Gd(MHE‐DTTA) and Gd(BME‐DTTA) were found to be 15.27 ± 2.21 and 16.78 ± 0.36, respectively. LD50 of both compounds was >0.2 mmol/kg. These stabilities and lower limits of LD50 indicate the possible in vivo application of these agents. © 1991 Academic Press, Inc. Copyright © 1991 Wiley‐Liss, Inc., A Wiley Company