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Intraoperative ¹⁸⁶Re-Liposome Radionuclide Therapy in a Head and Neck Squamous Cell Carcinoma Xenograft Positive Surgical Margin Model

Authors' Affiliations: Departments of ¹ Otolaryngology-Head and Neck Surgery and ² Radiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas

Requests for reprints: Ande Bao, Department of Otolaryngology-Head and Neck Surgery, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900. Phone: 210-567-5657; Fax: 210-567-3617; E-mail: bao{at}uthscsa.edu.

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 β-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.

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