Clearance of liposomal gadolinium: In vivo decomplexation

Abstract

The contrast agents gadolinium-DTPA (diethylenetriaminepentaacetic acid), Gd-DOTA (tetraazacyclododecanetetraacetic acid), and Gd-HP-DO3A (1,4,7-tris[carboxymethyl]-10-[2′hydroxypropyl]-1,4,7,10-tetraazacyclododecane) are used in humans as extracellular contrast agents. Although free Gd⁺ ion is toxic, the intact Gd³⁺ complexes are rapidly excreted and are relatively nontoxic. Decomplexation with release of free gadolinium is a relevant clinical concern in patients with altered renal clearance. Blood pool contrast agents currently under development may have longer clearance half-lives and be more prone to decomplexation. The present study was designed to evaluate the clearance of liposomally encapsulated Gd³⁺ complexes (DTPA, DOTA, and HP-DO3A). The macrocyclic compounds had more rapid and complete clearance than DTPA (P <.05). Parallel studies with carbon-14 and Gd-153-labeled complexes showed significant differences (P <.05) in the amount of these isotopes retained in the heart, kidney, lungs, and spleen, providing strong supportive evidence for in vivo decomplexation.