Synthesis, Structure and Contrast Efficacy of Bismuth (III) Chelated with 1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetramethylene Phosphonate and its Incorporation into Nano-Assembled Capsules

摘要

Medical imaging now plays an integral role in the diagnosis and treatment of illness. The use of contrast agents in molecular imaging has been instrumental in the diagnosis of cancer and similar pathologies. The incorporation of lanthanide-based contrast agents employed in magnetic resonance imaging (MRI) into nano-assembled capsules (NACs) have shown potential utility for improved contrast in MRI by slowing the tumbling of the polyanionic paramagnetic metal ions. The utility of NACs was herein extended to computed tomography (CT) imaging by the incorporation of electron dense bismuth (III)-based chelates into NACs in order to provide a high payload of agent in relatively small volumes. Bismuth (III) was chelated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonate (DOTP) and incorporated into a NAC encapsulated with a spherical silica nanoparticle shell at varied concentrations, solvent systems and temperature. The size distribution of these NACs was characterized and compared to gadolinium-based NACs. The formation of bismuth containing NACs was confirmed; the reproducibility in size distribution was not as reproducible as expected, and did not adhere to the same trends as lanthanide containing capsules. Although aging time may be directly related to size distribution of the capsules, the solvent system and temperature studies did not yield a consistent relationship.