Tumor uptake of hollow gold nanospheres after intravenous and intra-arterial injection: PET/CT study in a rabbit VX2 liver cancer model

Mol Imaging Biol. 2013 Oct;15(5):614-24. doi: 10.1007/s11307-013-0635-x.

Abstract

Purpose: This study was designed to investigate the intratumoral uptake of hollow gold nanospheres (HAuNS) after hepatic intra-arterial (IA) and intravenous (IV) injection in a liver tumor model.

Materials and methods: Fifteen VX2 tumor-bearing rabbits were randomized into five groups (n = 3 in each group) that received either IV (64)Cu-labeled PEG-HAuNS (IV-PEG-HAuNS), IA (64)Cu-labeled PEG-HAuNS (IA-PEG-HAuNS), IV cyclic peptide (RGD)-conjugated (64)Cu-labeled PEG-HAuNS (IV-RGD-PEG-HAuNS), IA RGD-conjugated (64)Cu-labeled PEG-HAuNS (IA-RGD-PEG-HAuNS), or IA (64)Cu-labeled PEG-HAuNS with lipiodol (IA-PEG-HAuNS-lipiodol). The animals underwent PET/CT 1 h after injection, and uptake expressed as percentage of injected dose per gram of tissue (%ID/g) was measured in tumor and major organs. The animals were euthanized 24 h after injection, and tissues were evaluated for radioactivity.

Results: At 1 h after injection, animals in the IA-PEG-HAuNS-lipiodol group showed significantly higher tumor uptake (P < 0.001) and higher ratios of tumor-to-normal liver uptake (P < 0.001) than those in all other groups. The biodistribution of radioactivity 24 h after injection showed that IA delivery of PEG-HAuNS with lipiodol resulted in the highest tumor uptake (0.33 %ID/g; P < 0.001) and tumor-to-normal liver ratio (P < 0.001) among all delivery methods. At 24 h, the IA-RGD-PEG-HAuNS group showed higher tumor uptake than the IA-PEG-HAuNS group (0.20 vs. 0.099 %ID/g; P < 0.001).

Conclusion: Adding iodized oil to IA-PEG-HAuNS maximizes nanoparticle delivery to hepatic tumors and therefore may be useful in targeted chemotherapy and photoablative therapy. PET/CT can be used to noninvasively monitor the biodistribution of radiolabeled HAuNS after IV or IA injection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gold / administration & dosage
  • Gold / metabolism*
  • Injections, Intra-Arterial
  • Injections, Intravenous
  • Liver Neoplasms / diagnostic imaging*
  • Liver Neoplasms / pathology
  • Nanospheres / metabolism*
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry
  • Positron-Emission Tomography*
  • Rabbits
  • Tissue Distribution
  • Tomography, X-Ray Computed*
  • Whole Body Imaging

Substances

  • Oligopeptides
  • Polyethylene Glycols
  • Gold
  • arginyl-glycyl-aspartic acid