Gadolinium, neodymium, praseodymium, thulium and ytterbium complexes as potential contrast enhancing agents for NMR imaging

Abstract

Complexes of ferric (3) and gadolinium (5) citrate, gadolinium tricarballylate (6) and complexes of gadolinium, neodymium, praseodymium, thulium and ytterbium with complexons EDTA (7), CDTA (8), EGTA (9), DTPA (10) and TTHA (11) were synthesized and evaluated as potential contrast enhancing agents for NMR imaging by measuring their stability constants and their effectiveness in eliciting spin-lattice ( T 1) and spin-spin ( T 2) relaxations of protons in water and plasma. High stability constants (log 10 k = 22 or higher) and excellent relaxation properties were found for Gd-EGTA 19, Yb-EGTA 20, Gd-DTPA 23, Yb-DTPA 24, Gd-TTHA 28, Yb-TTHA 29 and Tm-TTHA 30. These compounds were considered as potential intravenous contrast agents for NMR imaging. Whereas, the stability constant of 28 was higher (log 10 k = 28.4) than that (log 10 k = 22.4) of the clinically used 23, the LD 50 value, using Swiss male mice, for 28 was lower (2.88 mmol/kg) than that for 23 (3.74 mmol/kg). The somewhat higher toxicity of 28 than that of 23 was explained by a higher osmolality of 28 as compared to 23. The gadolinium citrate 5 and gadolinium tricarballylate 6 were proposed as potential oral contrast agents.