title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA. xieh@tsu.edu
authors.forename: Huan
authors.initials: H
authors.lastname: Xie
authors.forename: Beth
authors.initials: B
authors.lastname: Goins
authors.forename: Ande
authors.initials: A
authors.lastname: Bao
authors.forename: Zheng Jim
authors.initials: ZJ
authors.lastname: Wang
authors.forename: William T
authors.initials: WT
authors.lastname: Phillips
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000532:radiotherapy; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005240:Feasibility Studies; D006046:Gold; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D064847:Multimodal Imaging; D050997:Nanomedicine; D057145:Nanoshells / Q000008:administration & dosage*; D049268:Positron-Emission Tomography; D051381:Rats; D011923:Rats, Nude; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays
chemical_list: D003301:Copper Radioisotopes; D006046:Gold