title: First clinical results of (D)-18F-Fluoromethyltyrosine (BAY 86-9596) PET/CT in patients with non-small cell lung cancer and head and neck squamous cell carcinoma.
abstract: (D)-(18)F-fluoromethyltyrosine (d-(18)F-FMT), or BAY 86-9596, is a novel (18)F-labeled tyrosine derivative rapidly transported by the l-amino acid transporter (LAT-1), with a faster blood pool clearance than the corresponding l-isomer. The aim of this study was to demonstrate the feasibility of tumor detection in patients with non-small cell lung cancer (NSCLC) or head and neck squamous cell cancer (HNSCC) compared with inflammatory and physiologic tissues in direct comparison to (18)F-FDG.
  
  
  METHODS
  18 patients with biopsy-proven NSCLC (n = 10) or HNSCC (n = 8) were included in this Institutional Review Board-approved, prospective multicenter study. All patients underwent (18)F-FDG PET/CT scans within 21 d before d-(18)F-FMT PET/CT. For all patients, safety and outcome data were assessed.
  
  
  RESULTS
  No adverse reactions were observed related to d-(18)F-FMT. Fifty-two lesions were (18)F-FDG-positive, and 42 of those were malignant (34 histologically proven and 8 with clinical reference). Thirty-two of the 42 malignant lesions were also d-(18)F-FMT-positive, and 10 lesions had no tracer uptake above the level of the blood pool. Overall there were 34 true-positive, 8 true-negative, 10 false-negative, and only 2 false-positive lesions for d-(18)F-FMT, whereas (18)F-FDG was true-positive in 42 lesions, with 10 false-positive and only 2 false-negative, resulting in a lesion-based detection rate for d-(18)F-FMT and (18)F-FDG of 77% and 95%, respectively, with an accuracy of 78% for both tracers. A high d-(18)F-FMT tumor-to-blood pool ratio had a negative correlation with overall survival (P = 0.050), whereas the (18)F-FDG tumor-to-blood pool ratio did not correlate with overall survival.
  
  
  CONCLUSIONS
  d-(18)F-FMT imaging in patients with NSCLC and HNSCC is safe and feasible. The presented preliminary results suggest a lower sensitivity but higher specificity for d-(18)F-FMT over (18)F-FDG, since there is no d-(18)F-FMT uptake in inflammation. This increased specificity may be particularly beneficial in areas with endemic granulomatous disease and may improve clinical management. Further clinical investigations are needed to determine its clinical value and relevance for the prediction of survival prognosis.
authors.affiliation: Division of Nuclear Medicine, Department of Medical Radiology, University Hospital of Zurich, Zurich, Switzerland irene.burger@usz.ch.
authors.forename: Irene A
authors.initials: IA
authors.lastname: Burger
authors.affiliation: Bayer Healthcare AG, Berlin, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Zitzmann-Kolbe
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Pruim
authors.affiliation: Piramal Imaging GmbH, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Friebe
authors.affiliation: Bayer Healthcare AG, Berlin, Germany.
authors.forename: Keith
authors.initials: K
authors.lastname: Graham
authors.affiliation: Piramal Imaging GmbH, Berlin, Germany.
authors.forename: Andrew
authors.initials: A
authors.lastname: Stephens
authors.affiliation: Piramal Imaging GmbH, Berlin, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Dinkelborg
authors.affiliation: Bayer Healthcare AG, Berlin, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Kowal
authors.affiliation: Center for Radiopharmaceutical Sciences of ETH, PSI, and USZ, ETH Zurich, Zurich, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Luurtsema
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Bram
authors.initials: B
authors.lastname: Maas
authors.affiliation: Department of Thoracic Surgery, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Michaela
authors.initials: M
authors.lastname: Horn-Tutic
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University Hospital of Bale, Bale, Switzerland.
authors.forename: Stephan K
authors.initials: SK
authors.lastname: Haerle
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Wiegers
authors.affiliation: Division of Nuclear Medicine, Department of Medical Radiology, University Hospital of Zurich, Zurich, Switzerland Division of Medical Oncology, Department of Internal Medicine, University Hospital of Zurich, Zurich, Switzerland; and.
authors.forename: Niklaus G
authors.initials: NG
authors.lastname: Schaefer
authors.affiliation: MRI Stadelhofen, Zurich, Switzerland.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Hany
authors.affiliation: Division of Nuclear Medicine, Department of Medical Radiology, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Gustav K
authors.initials: GK
authors.lastname: von Schulthess
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000000981:diagnostic imaging*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000000981:diagnostic imaging*; D005189:False Positive Reactions; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging*; D006801:Humans; D007249:Inflammation; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry*
chemical_list: D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D014443:Tyrosine
keywords: FDG; LAT-1; d-amino acid transport system; specificity; tumor staging