Gas-Filled Phospholipid Nanoparticles Conjugated with Gadolinium Play a Role as a Potential Theragnostics for MR-Guided HIFU Ablation

To develop a long-circulating theragnostics, meaning therapeutics and diagnostics for MR-guided HIFU ablation, we designed and prepared Gd-C(5)F(12)-phospholipid nanobubbles (PLNs) 30–100 nm in diameter. The biochemical and physical characterization of Gd-C(5)F(12)-PLNs were performed. Since Gd-C(5)F(12)-PLN-50 (Φ = 50 nm) and Gd-C(5)F(12)-PLN-100 (Φ = 100 nm) enhanced the hyperthermal effect of HIFU size- and concentration-dependently in a tissue-mimicking phantom, its circulation, distribution, tumor accumulation and tumor ablation were examined in tumor-bearing mice. The plasma-half life of Gd-C(5)F(12)-PLNs was longer than 1.5 hrs. Gd-C(5)F(12)-PLNs mainly accumulated in the liver and the spleen, suggesting that they are slowly secreted through the hepatobiliary pathway. Monitored by the T1 signal intensity of MR, Gd-C(5)F(12)-PLNs accumulated in tumor tissues for 8 hours in mice. HIFU with Gd-C(5)F(12)-PLN-100 showed the increased tumor ablation area as compared with HIFU alone. The results suggest that Gd-C(5)F(12)-PLNs exhibit a potential theragnostics for MR-guided HIFU ablation.