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


METHODS
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.
Department of Otolaryngology-Head and Neck Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Sean X
SX
Wang
Ande
A
Bao
Stephanie J
SJ
Herrera
William T
WT
Phillips
Beth
B
Goins
Cristina
C
Santoyo
Frank R
FR
Miller
Randal A
RA
Otto
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D003131:Combined Modality Therapy; D005029:Ethylenediamines / Q000008:administration & dosage*; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D006801:Humans; D007430:Intraoperative Care / Q000379:methods*; D008081:Liposomes / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D009942:Organometallic Compounds / Q000008:administration & dosage*; D011879:Radiotherapy Dosage; D051381:Rats; D011923:Rats, Nude; D012211:Rhenium / Q000008:administration & dosage* / Q000737:chemistry; D047368:Tumor Burden / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
C521828:188Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine; D005029:Ethylenediamines; D008081:Liposomes; D009942:Organometallic Compounds; D012211:Rhenium