Intraoperative 186Re-liposome radionuclide therapy in a head and neck squamous cell carcinoma xenograft positive surgical margin model.

Abstract

PURPOSE:

Positive surgical margins in advanced head and neck squamous cell carcinoma (HNSCC) have a well-documented association with an increased risk of locoregional recurrence and significantly poorer survival. Traditionally, unresectable tumor is treated with postoperative radiotherapy and/or chemotherapy. However, these therapeutic options can delay treatment and increase toxicity. The potential value of intraoperative injection of liposomal therapeutic radionuclides as a locoregional, targeted therapy in unresectable advanced HNSCC was assessed in a nude rat xenograft positive surgical margin model.

EXPERIMENTAL DESIGN:

The therapeutic effects of beta-emission rhenium-186 (186Re) carried by liposomes into the tumor remnants in a nude rat squamous cell carcinoma xenograft model were studied. Following the partial resection of tumor xenografts, the animals were intratumorally injected with 186Re-labeled or unlabeled (control) neutrally charged or positively charged 100-nm-diameter liposomes. Tumor size, body weight, hematology, and toxicity were monitored for 35 days posttherapy.

RESULTS:

The neutral (n = 4) and cationic (n = 4) liposome control groups showed an increase in tumor growth of 288.0 +/- 37.3% and 292.2 +/- 133.7%, respectively, by day 15. The 186Re-neutral-liposome group (n = 8) and the 186Re-cationic-liposome group (n = 8) presented with an average final tumor volume of 25.6 +/- 21.8% and 28.5 +/- 32.2%, respectively, at the end of the study (day 35). All groups showed consistent increases in body weight. No significant systemic toxicity was observed in any of the animals.

CONCLUSIONS:

With excellent tumor suppression and minimal side-effect profile, the intraoperative use of liposomal therapeutic radionuclides may play a role in the management of positive surgical margins in advanced HNSCC.

• Authors: Sean X Wang, Ande Bao, Stephanie J Herrera, William T Phillips, Beth Goins, Cristina Santoyo, Frank R Miller, Randal A Otto
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 12 Pg. 3975-83 (Jun 15 2008) ISSN: 1078-0432 [Print] United States
• PMID: 18559620 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• 188Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine
• Ethylenediamines
• Liposomes
• Organometallic Compounds
• Rhenium

Topics

• Animals
• Carcinoma, Squamous Cell (pathology, radiotherapy, surgery)
• Combined Modality Therapy
• Ethylenediamines (administration & dosage)
• Head and Neck Neoplasms (pathology, radiotherapy, surgery)
• Humans
• Intraoperative Care (methods)
• Liposomes (chemistry, therapeutic use)
• Male
• Organometallic Compounds (administration & dosage)
• Radiotherapy Dosage
• Rats
• Rats, Nude
• Rhenium (administration & dosage, chemistry)
• Tumor Burden (radiation effects)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays