Clearance of liposomal gadolinium: In vivo decomplexation

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.