Tumor accumulation of gadolinium in lipid-nanoparticles intravenously injected for neutron-capture therapy of cancer

Abstract

Gadolinium-incorporating lipid-nanoemulsions (Gd-nanoLE) for neutron-capture therapy were prepared. As a more convenient administration route than the intraperitoneal (i.p.) injection previously reported, the intravenous (i.v.) injections in tumor-bearing hamsters were carried out at an administration volume of 1 ml, which was the maximum tolerable injection volume of an i.v. injection and half that of an i.p. injection. When the standard-Gd-nanoLE of 1.5 mg Gd/ml was administered, the absolute bioavailability in the i.p. injection was 57%, probably resulting from incomplete absorption from the peritoneal cavity into the blood stream. The biodistribution data revealed that the i.v. injection had three advantages over the i.p. injection, namely, a faster and higher accumulation of Gd-nano LE, and a more extended retention time in the tumor. Two i.v. injections of the standard-Gd-nanoLE with a 24 h interval doubled the tumor accumulation of Gd, resulting in 49.7 μg Gd/g wet tumor 12 h after administration. By using a twofold Gd-enriched formulation (High-Gd-nanoLE) of 3.0 mg Gd/ml in the repeated administration schedule, the accumulation was doubled again, reaching 101 μg Gd/g wet tumor. This level was comparable to the maximum level in the single i.p. injection previously reported. These results demonstrated that i.v. injection could be an alternative to i.p. injection as an administration route.