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

J Nucl Med. 2014 Nov;55(11):1778-85. doi: 10.2967/jnumed.114.140699. Epub 2014 Sep 25.

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.

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.

Keywords: FDG; LAT-1; d-amino acid transport system; specificity; tumor staging.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging*
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / diagnostic imaging*
  • False Positive Reactions
  • Female
  • Fluorine Radioisotopes / chemistry*
  • Fluorodeoxyglucose F18 / chemistry
  • Head and Neck Neoplasms / diagnosis
  • Head and Neck Neoplasms / diagnostic imaging*
  • Humans
  • Inflammation
  • Kaplan-Meier Estimate
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / diagnostic imaging*
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Prognosis
  • Prospective Studies
  • Sensitivity and Specificity
  • Tomography, X-Ray Computed
  • Tyrosine / analogs & derivatives*
  • Tyrosine / chemistry*

Substances

  • Fluorine Radioisotopes
  • Fluorodeoxyglucose F18
  • Tyrosine