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 ( 64 Cu). Intratumoral infusion of 64 Cu-nanoshells and two controls, ie, 64 Cu-DOTA (1,4,7,10-tetraazaciclododecane-1,4,7,10-tetraacetic acid) and 64 Cu-DOTA-PEG (polyethylene glycol), as well as intravenous injection of 64 Cu-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 Cu-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 Cu-nanoshells. Positron emission tomography images and organ biodistribution results on rats after intratumoral administration showed higher retention of 64 Cu-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 Cu-nanoshells improved substantially and were stable at 44 hours post-injection. Conclusion: There was a higher intratumoral retention of 64 Cu-nanoshells and a lower concentration in other healthy tissues, suggesting that intratumoral administration is a potentially better approach for nanoshell-based photothermal therapy.

Intratumorally Injected 177Lu-Labeled Gold Nanoparticles: Gold Nanoseed Brachytherapy with Application for Neoadjuvant Treatment of Locally Advanced Breast Cancer

“…5), likely due to its poor tumor retention. Similar results were reported by Xie et al for intratumorally injected nontargeted 64 Cu-labeled gold nanoshells, which were retained in head and neck squamous cell carcinoma xenografts in nude rats, whereas 64 Cu-DOTA or 64 Cu-DOTA-PEG not linked to the gold nanoshells were cleared from these tumors over 44 h (25). Liver and spleen uptake remains a major challenge to the use of systemically administered AuNP for cancer treatment (26), but this obstacle was overcome using intratumorally injected 177 Lu-T-AuNP and 177 Lu-NT-AuNP.…”

The morpho-functional assessment of plasmonic photothermal therapy effects on transplanted liver tumor

“…An hour before laser irradiation, the animals were injected intratumorally with the solution of gold nanorods in the amount of 30% of the tumor volume. The injection of the gold nanoparticles directly into the tumor was conducted according to the paper of Xie and co-workers, 24 where the authors demonstrated that using such a modi¯cation of intratumoral injection leads to prolonged retention of nanoparticles in tumor tissue.…”

Cancer Cell Damage at Laser-Induced Plasmon-Resonant Photothermal Treatment of Transplanted Liver Tumor

“…An hour before laser irradiation, the animals were injected intratumorally by the solution of the gold nanorods in the amount of 30 % of the tumor volume. The injection of the gold nanoparticles directly into the tumor was conducted according to the paper by Xie and co-workers [18], where the authors demonstrated that using such modification of intratumoral injection leads to prolonged retention of nanoparticles in tumor tissue. The animals were irradiated with an 808-nm CW laser LS-2-N-808-10000 (Laser Systems, Ltd., St. Petersburg, Russia) at a power density …”