title: Therapeutic combination of radiolabeled CLR1404 with external beam radiation in head and neck cancer model systems.
abstract: OBJECTIVE
  CLR1404 is a phospholipid ether that exhibits selective uptake and retention in malignant tissues. Radiolabeled CLR1404 enables tumor-specific positron-emission tomography (PET) imaging ((124)I) and targeted delivery of ionizing radiation ((131)I). Here we describe the first preclinical studies of this diapeutic molecule in head and neck cancer (HNC) models.
  
  
  METHODS
  Tumor-selective distribution of (124)I-CLR1404 and therapeutic efficacy of (131)I-CLR1404 were tested in HNC cell lines and patient-derived xenograft tumor models. Monte Carlo dose calculations and (124)I-CLR1404 PET/CT imaging were used to examine (131)I-CLR1404 dosimetry in preclinical HNC tumor models.
  
  
  RESULTS
  HNC tumor xenograft studies including patient-derived xenografts demonstrate tumor-selective uptake and retention of (124)I-CLR1404 resulting in a model of highly conformal dose distribution for (131)I-CLR1404. We observe dose-dependent response to (131)I-CLR1404 with respect to HNC tumor xenograft growth inhibition and this effect is maintained together with external beam radiation.
  
  
  CONCLUSIONS
  We confirm the utility of CLR1404 for tumor imaging and treatment of HNC. This promising agent warrants further investigation in a developing phase I trial combining (131)I-CLR1404 with reduced-dose external beam radiation in patients with loco-regionally recurrent HNC.
authors.affiliation: Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, United States.
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Morris
authors.affiliation: Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, United States.
authors.forename: Jamey P
authors.initials: JP
authors.lastname: Weichert
authors.affiliation: Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, United States.
authors.forename: Jarob
authors.initials: J
authors.lastname: Saker
authors.affiliation: Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, United States.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Armstrong
authors.affiliation: Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, United States.
authors.forename: Abigail
authors.initials: A
authors.lastname: Besemer
authors.affiliation: Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, United States.
authors.forename: Bryan
authors.initials: B
authors.lastname: Bednarz
authors.affiliation: Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, United States.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Kimple
authors.affiliation: Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, United States. Electronic address: harari@humonc.wisc.edu.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Harari
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D007462:Iodobenzenes / Q000494:pharmacology*; D008297:Male; D008819:Mice, Nude; D008954:Models, Biological; D009010:Monte Carlo Method; D009368:Neoplasm Transplantation / Q000379:methods; D010742:Phospholipid Ethers / Q000494:pharmacology*; D049268:Positron-Emission Tomography / Q000379:methods; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D014057:Tomography, X-Ray Computed / Q000379:methods; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: C000599353:CLR1404; D007462:Iodobenzenes; D010742:Phospholipid Ethers; D019275:Radiopharmaceuticals
keywords: CLR1404; Diapeutic; Head and neck cancer; Radiation; Radionuclide