Irene A Burger1, Sabine Zitzmann-Kolbe2, Jan Pruim3, Matthias Friebe4, Keith Graham2, Andrew Stephens4, Ludger Dinkelborg4, Kristin Kowal2, Roger Schibli5, Gert Luurtsema3, Bram Maas3, Michaela Horn-Tutic6, Stephan K Haerle7, Johan Wiegers3, Niklaus G Schaefer8, Thomas F Hany9, Gustav K von Schulthess10. 1. Division of Nuclear Medicine, Department of Medical Radiology, University Hospital of Zurich, Zurich, Switzerland irene.burger@usz.ch. 2. Bayer Healthcare AG, Berlin, Germany. 3. Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands. 4. Piramal Imaging GmbH, Berlin, Germany. 5. Center for Radiopharmaceutical Sciences of ETH, PSI, and USZ, ETH Zurich, Zurich, Switzerland. 6. Department of Thoracic Surgery, University Hospital of Zurich, Zurich, Switzerland. 7. Department of Otolaryngology-Head and Neck Surgery, University Hospital of Bale, Bale, Switzerland. 8. 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. 9. MRI Stadelhofen, Zurich, Switzerland. 10. Division of Nuclear Medicine, Department of Medical Radiology, University Hospital of Zurich, Zurich, Switzerland.
Abstract
UNLABELLED: (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. CONCLUSION: 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.
UNLABELLED: (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. CONCLUSION: 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: Mohamed Hassanein; Matthew R Hight; Jason R Buck; Mohammed N Tantawy; Michael L Nickels; Megan D Hoeksema; Bradford K Harris; Kelli Boyd; Pierre P Massion; H Charles Manning Journal: Mol Imaging Biol Date: 2016-02 Impact factor: 3.488
Authors: Athanasios S Theodoropoulos; Ioannis Gkiozos; Georgios Kontopyrgias; Adrianni Charpidou; Elias Kotteas; George Kyrgias; Maria Tolia Journal: SAGE Open Med Date: 2020-09-28