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)-18F-fluoromethyltyrosine (D-18F-FMT), or BAY 86-9596, is a novel 18F-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 18F-FDG. Methods: 18 patients with biopsyproven NSCLC (n 5 10) or HNSCC (n 5 8) were included in this Institutional Review Board-approved, prospective multicenter study. All patients underwent 18F-FDG PET/CT scans within 21 d before D-18F-FMT PET/CT. For all patients, safety and outcome data were assessed. Results: No adverse reactions were observed related to D-18F-FMT. Fifty-two lesions were 18F-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-18FFMT- 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-18FFMT, whereas 18F-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-18F-FMT and 18F-FDG of 77% and 95%, respectively, with an accuracy of 78% for both tracers. A high D-18F-FMT tumor-to-blood pool ratio had a negative correlation with overall survival (P 5 0.050), whereas the 18F-FDG tumor-to-blood pool ratio did not correlate with overall survival. Conclusion: D-18FFMT imaging in patients with NSCLC and HNSCC is safe and feasible. The presented preliminary results suggest a lower sensitivity but higher specificity for D-18F-FMT over 18F-FDG, since there is no D-18F-FMT uptake in inflammation. This increased specificity may be particularly beneficial in areas with endemic granulomatous disease and may improve linical management. Further clinical investigations are needed to determine its clinical value and relevance for the prediction of survival prognosis.