title: Multimodal Image-Guided Surgical and Photodynamic Interventions in Head and Neck Cancer: From Primary Tumor to Metastatic Drainage.
abstract: OBJECTIVE
  The low survival rate of head and neck cancer (HNC) patients is attributable to late disease diagnosis and high recurrence rate. Current HNC staging has inadequate accuracy and low sensitivity for effective diagnosis and treatment management. The multimodal porphyrin lipoprotein-mimicking nanoparticle (PLP), intrinsically capable of positron emission tomography (PET), fluorescence imaging, and photodynamic therapy (PDT), shows great potential to enhance the accuracy of HNC staging and potentially HNC management.
  
  
  METHODS
  Using a clinically relevant VX-2 buccal carcinoma rabbit model that is able to consistently develop metastasis to regional lymph nodes after tumor induction, we investigated the abilities of PLP for HNC diagnosis and management.
  
  
  RESULTS
  PLPs facilitated accurate detection of primary tumor and metastatic nodes (their PET image signal to surrounding muscle ratios were 10.0 and 7.3, respectively), and provided visualization of the lymphatic drainage from tumor to regional lymph nodes by both preoperative PET and intraoperative fluorescence imaging, allowing the identification of unknown primaries and recurrent tumors. PLP-PDT significantly enhanced cell apoptosis in mouse tumors (73.2% of PLP-PDT group vs 7.1% of PLP alone group) and demonstrated complete eradication of primary tumors and obstruction of tumor metastasis in HNC rabbit model without toxicity in normal tissues or damage to adjacent critical structures.
  
  
  CONCLUSIONS
  PLPs provide a multimodal imaging and therapy platform that could enhance HNC diagnosis by integrating PET/computed tomography and fluorescence imaging, and improve HNC therapeutic efficacy and specificity by tailoring treatment via fluorescence-guided surgery and PDT.
authors.affiliation: Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Canada. Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, Canada.
authors.forename: Nidal
authors.initials: N
authors.lastname: Muhanna
authors.affiliation: Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Canada. Medical Isotopes Research Center, Peking University, Beijing, China.
authors.forename: Liyang
authors.initials: L
authors.lastname: Cui
authors.affiliation: Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Canada. Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, Canada.
authors.forename: Harley
authors.initials: H
authors.lastname: Chan
authors.affiliation: Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Burgess
authors.affiliation: Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Canada. Department of Pharmaceutical Sciences, University of Toronto, Toronto, Canada. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada.
authors.forename: Cheng S
authors.initials: CS
authors.lastname: Jin
authors.affiliation: Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Canada. Department of Pharmaceutical Sciences, University of Toronto, Toronto, Canada.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: MacDonald
authors.affiliation: Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Huynh
authors.affiliation: Medical Isotopes Research Center, Peking University, Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Canada. gang.zheng@uhnres.utoronto.ca Jonathan.Irish@uhn.ca juan.chen@uhnresearch.ca.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Canada. Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, Canada. gang.zheng@uhnres.utoronto.ca Jonathan.Irish@uhn.ca juan.chen@uhnresearch.ca.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Irish
authors.affiliation: Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Canada. Department of Pharmaceutical Sciences, University of Toronto, Toronto, Canada. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada. gang.zheng@uhnres.utoronto.ca Jonathan.Irish@uhn.ca juan.chen@uhnresearch.ca.
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D045744:Cell Line, Tumor; D002788:Cholesterol Esters / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004134:Dimyristoylphosphatidylcholine / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008207:Lymphatic Metastasis; D053758:Nanoparticles / Q000008:administration & dosage; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011166:Porphyrins / Q000008:administration & dosage; D011817:Rabbits; D025321:Surgery, Computer-Assisted; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D002788:Cholesterol Esters; D017319:Photosensitizing Agents; D011166:Porphyrins; C014409:cholesteryl oleate; D004134:Dimyristoylphosphatidylcholine