title: Ultrasound-stimulated drug delivery for treatment of residual disease after incomplete resection of head and neck cancer.
abstract: Microbubbles triggered with localized ultrasound (US) can improve tumor drug delivery and retention. Termed US-stimulated drug delivery, this strategy was applied to head and neck cancer (HNC) in a post-surgical tumor resection model. Luciferase-positive HNC squamous cell carcinoma (SCC) was implanted in the flanks of nude athymic mice (N = 24) that underwent various degrees of surgical tumor resection (0%, 50% or 100%). After surgery, animals received adjuvant therapy with cetuximab-IRDye alone, or cetuximab-IRDye in combination with US-stimulated drug delivery or saline injections (control) on days 4, 7 and 10. Tumor drug delivery was assessed on days 0, 4, 7, 10, 14 and 17 with an in vivo fluorescence imaging system, and tumor viability was evaluated at the same times with in vivo bioluminescence imaging. Tumor caliper measurements occurred two times per week for 24 d. Optical imaging revealed that in the 50% tumor resection group, US-stimulated drug delivery resulted in a significant increase in cetuximab delivery compared with administration of drug alone on day 10 (day of peak fluorescence) (p = 0.03). Tumor viability decreased in all groups that received cetuximab-IRDye in combination with US-stimulated drug delivery, compared with the group that received only the drug. After various degrees of surgical resection, this novel study reports positive improvements in drug uptake in the residual cancer cells when drug delivery is stimulated with US.
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Anna G
authors.initials: AG
authors.lastname: Sorace
authors.affiliation: Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Korb
authors.affiliation: Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Warram
authors.affiliation: Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama, USA; Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Heidi
authors.initials: H
authors.lastname: Umphrey
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama, USA; Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Electrical & Computer Engineering, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Zinn
authors.affiliation: Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA; Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Eben
authors.initials: E
authors.lastname: Rosenthal
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama, USA; Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Electrical & Computer Engineering, University of Alabama at Birmingham, Birmingham, Alabama, USA. Electronic address: hoyt@uab.edu.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hoyt
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D045744:Cell Line, Tumor; D000068818:Cetuximab; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000528:radiation effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018365:Neoplasm, Residual; D013010:Sonication / Q000379:methods*; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D000068818:Cetuximab
keywords: Adjuvant therapy; Cetuximab; Drug delivery; Head and neck cancer; Microbubbles; Optical imaging; Ultrasound