Effect of intratumoral administration on biodistribution of 64Cu-labeled nanoshells

Huan Xie, Beth Goins, Ande Bao, Zheng Jim Wang, William T. Phillips

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Background: Gold nanoshells are excellent agents for photothermal ablation cancer therapy and are currently under clinical trial for solid tumors. Previous studies showed that passive delivery of gold nanoshells through intravenous administration resulted in limited tumor accumulation, which represents a major challenge for this therapy. In this report, the impact of direct intratumoral administration on the pharmacokinetics and biodistribution of the nanoshells was systematically investigated. Methods: The gold nanoshells were labeled with the radionuclide, copper-64 (64). Intratumoral infusion of 64-nanoshells and two controls, ie, 64-DOTA (1,4,7,10-tetraazaciclododecane- 1,4,7,10-tetraacetic acid) and 64-DOTA-PEG (polyethylene glycol), as well as intravenous injection of 64-nanoshells were performed in nude rats, each with a head and neck squamous cell carcinoma xenograft. The pharmacokinetics was determined by radioactive counting of serial blood samples collected from the rats at different time points post-injection. Using positron emission tomography/computed tomography imaging, the in vivo distribution of 64-nanoshells and the controls was monitored at various time points after injection. Organ biodistribution in the rats at 46 hours was analyzed by radioactive counting and compared between the different groups. Results: The resulting pharmacokinetic curves indicated a similar trend between the intratumorally injected agents, but a significant difference with the intravenously injected 64-nanoshells. Positron emission tomography images and organ biodistribution results on rats after intratumoral administration showed higher retention of 64-nanoshells in tumors and less concentration in other healthy organs, with a significant difference from the controls. It was also found that, compared with intravenous injection, tumor concentrations of 64-nanoshells improved substantially and were stable at 44 hours post-injection. Conclusion: There was a higher intratumoral retention of 64-nanoshells and a lower concentration in other healthy tissues, suggesting that intratumoral administration is a potentially better approach for nanoshell-based photothermal therapy.

Original languageEnglish (US)
Pages (from-to)2227-2238
Number of pages12
JournalInternational journal of nanomedicine
Volume7
DOIs
StatePublished - 2012

Keywords

  • Biodistribution
  • Gold nanoshells
  • Intratumoral administration
  • Positron emission tomography

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

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