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

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 (⁶⁴Cu). Intratumoral infusion of ⁶⁴Cu-nanoshells and two controls, ie, ⁶⁴Cu-DOTA (1,4,7,10-tetraazaciclododecane- 1,4,7,10-tetraacetic acid) and ⁶⁴Cu-DOTA-PEG (polyethylene glycol), as well as intravenous injection of ⁶⁴Cu-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 ⁶⁴Cu-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 ⁶⁴Cu-nanoshells. Positron emission tomography images and organ biodistribution results on rats after intratumoral administration showed higher retention of ⁶⁴Cu-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 ⁶⁴Cu-nanoshells improved substantially and were stable at 44 hours post-injection.

Conclusion

There was a higher intratumoral retention of ⁶⁴Cu-nanoshells and a lower concentration in other healthy tissues, suggesting that intratumoral administration is a potentially better approach for nanoshell-based photothermal therapy.

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Keywords:

• gold nanoshells
• intratumoral administration
• positron emission tomography
• biodistribution

Acknowledgments

This work was performed under funding from Nanospectra Biosciences Inc, through NIST ATP Cooperative Agreement Number 70NANB4H3040. We thank the Pharmaceutical Research and Manufacturers of America Foundation and NIH/RTRN grant (5U54RR022762-05) to support the work of HX.

Disclosure

The authors report no conflicts of interest in this work.