Stability of MRI paramagnetic contrast media - A proton relaxometric protocol for transmetallation assessment

RATIONALE AND OBJECTIVES, The suitability of paramagnetic complexes as magn etic resonance contrast agents depends on various factors such as their rel axivity, stability, selectivity, and the inertness toward transmetallation by endogenous ions, The transmetallation of a series of 18 gadolinium compl exes by the Zn2+ ion was studied in vitro by proton relaxometry. METHODS. Transmetallation was analyzed through the evolution of the paramag netic longitudinal relaxation rate of water protons at 37 degrees C in pH = 7 phosphate buffer solutions containing 2.5 mmol/L of the gadolinium compl exes and 2.5 mmol/L zinc chloride. The measurements were performed at 0.47 T over a period of at least 3 days. RESULTS. The results confirm the high stability of macrocyclic systems and a high sensitivity of Gd- diethylenetriaminepentaacetic acid (DTPA) derivat ives to transmetallation by Zn2+ ions. The decreasing order of stability wi th respect to metal exchange is as follows: Gd-macrocyclics > Gd-C-function alized DTPA > Gd-DTPA > primary and secondary Gd-DTPA bisamides, The ternar y bisamide analyzed in this study[Gd-DTPA-1,11-bisbismethylamino-1,11-dioxo -3,6,9-triaza-3,6,9-tris(carboxymethyl)undecane] is more stable than the pa rent compound Gd-DTPA. CONCLUSIONS. A Simple relaxometric protocol has been successfully developed to study the in vitro transmetallation process of gadolinium complexes. Th e importance of the functionalization and substitution of the DTPA-like com plexes is clearly shown.