Potential Oral Contrast Agents Research Articles

MRI Evaluation of potential gastrointestinal contrast media

Diluted ProHance [Gd(HP-DO3A), Squibb Diagnostics, Princeton, NJ], Sustacal (Meadjohnson, Evansville, IN), a nutritional drink, and a ProHance/Sustacal mixture have been investigated as potential oral contrast agents. At 2 T, T1-weighted (SE 500/20) images demonstrated hyperintense (positive) signal enhancement of rat GI tracts within 10 min after the ingestion of 2.0 mM Gd(HP-DO3A) or 2.0 mM ProHance/Sustacal. T2-weighted (SE 3000/80) images demonstrated hypointense (negative) signal intensity within 10 min after ingestion of 10 mM ProHance. Medical imaging applications of these oral contrast media are feasible.

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

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.

Work in progress: potential oral and intravenous paramagnetic NMR contrast agents.

The potential use of paramagnetic compounds as nuclear magnetic resonance (NMR) contrast agents was examined in vitro. The T1 relaxation times for serial dilutions of Cu2+, Cr3+, Fe3+, and Mn2+ ions in saline, gadolinium oxalate (a potential oral contrast agent) in suspension, and chromium EDTA (a potential intravenous contrast agent) in solution were determined. The effect on T1 of increasing the concentration of oxygen in solution was also examined. The relative magnitude of the decrease in T1 was, as expected, proportional to both the concentration of the paramagnetic substance and its effective magnetic moment. Thus NMR has the potential to detect differences in tissue oxygenation. By incorporating paramagnetic metal ions into insoluble compounds or stable complexes, toxicity can be dramatically reduced while maintaining a significant paramagnetic effect. Highly insoluble paramagnetic compounds or stable paramagnetic ion complexes can thus be utilized as effective NMR contrast agents with significantly diminished toxicity.