Ten-Gram-Scale Facile Synthesis of Organogadolinium Complex Nanoparticles for Tumor Diagnosis

The market of available contrast agents for clinical magnetic resonance imaging (MRI) has been dominated by gadolinium (Gd) chelates based T₁ contrast agents for decades. However, there are growing concerns about their safety because they are retained in the body and are nephrotoxic, which necessitated a warning by the U.S. Food and Drug Administration against the use of such contrast agents. To ameliorate these problems, it is necessary to improve the MRI efficiency of such contrast agents to allow the administration of much reduced dosages. In this study, a ten-gram-scale facile method is developed to synthesize organogadolinium complex nanoparticles (i.e., reductive bovine serum albumin stabilized Gd-salicylate nanoparticles, GdSalNPs-rBSA) with high r₁ value of 19.51 mm⁻¹ s⁻¹ and very low r₂/r₁ ratio of 1.21 (B₀ = 1.5 T) for high-contrast T₁-weighted MRI of tumors. The GdSalNPs-rBSA nanoparticles possess more advantages including low synthesis cost (≈0.54 USD per g), long in vivo circulation time (t_1/2 = 6.13 h), almost no Gd³⁺ release, and excellent biosafety. Moreover, the GdSalNPs-rBSA nanoparticles demonstrate excellent in vivo MRI contrast enhancement (signal-to-noise ratio (ΔSNR) ≈ 220%) for tumor diagnosis.