Abstract No. 171: Tumoral uptake of hollow gold nanospheres after intra-arterial and intravenous administration in an animal liver tumor model

Nanoparticles have been designed as a novel platform for delivery of anti-cancer agents. However, a major challenge for successful biomedical applications of nanoparticles is efficient delivery to target sites. This study was designed to investigate the tumoral uptake of hollow gold nanospheres (HAuNS) after intra-arterial (IA) and intravenous (IV) administration in an animal model. Rabbits with hepatic VX-2 tumors were randomized to 5 groups (n=3): 1) IV injection of 64Cu-HAuNS (IV-HAuNS); 2) IA injection of 64Cu-HAuNS (IA-HAuNS); 3) IV injection of 64Cu-HAuNS conjugated with tumor vessel specific cyclic peptide (RGD) (IV-RGD-HAuNS); 4) IA injection of RGD conjugated 64Cu-HAuNS (IA-RGD-HAuNS); or 5) IA delivery of 64Cu-HAuNS with ethiodol (IA-HAuNS-ethiodol). For the IA groups, the agents were injected into the hepatic artery. The animals were subjected to a PET-CT imaging 1 hour after administration and standard uptake values (SUV) were obtained from the tumor and normal liver. Animals were euthanized 24 hours after administration. Radioactivity in the tumor and liver tissue samples was measured with gamma counter; uptakes were calculated as percentage of injected dose per gram of tissue (%ID/g). PET-CT revealed that IA-HAuNS-ethiodol group animals had significantly higher tumor SUVs (p=0.0005) and higher tumor-to-liver ratios (p=0.0025) as compared to other groups. Tissue radioactivity measurements showed that IA delivery of HAuNS-ethiodol resulted in the highest tumor uptake (0.3319 %ID/g) among all delivery methods (p <0.0001). The tumor-to-liver ratio in IA-HAuNS-ethiodol group was about 2.7-fold as high as that in other groups. There were no differences in the tumor uptake between the IV-HAuNS and IA-HAuNS groups (p=0.81). IA-RGD-HAuNS group showed increased tumor uptake as compared to IA-HAuNS group (0.2014 %ID/g vs. 0.0099 %ID/g; p=0.0095). IA administration of HAuNS with ethiodol markedly increases tumor uptake and tumor-to-normal liver ratio as compared to all other methods. Addition of tumor vessel specific marker RGD to HAuNS increases tumor uptake after IA administration. PET-CT allows non-invasive monitoring of tumor uptake of radiolabeled HAuNS.