Fluorine-18-alpha-methyltyrosine positron emission tomography for diagnosis and staging of lung cancer: a clinicopathologic study

Clin Cancer Res. 2007 Nov 1;13(21):6369-78. doi: 10.1158/1078-0432.CCR-07-1294.

Abstract

Purpose: L-[3-(18)F]-alpha-methyltyrosine ([(18)F]FMT) is an amino acid tracer for positron emission tomography (PET). We evaluated the diagnostic usefulness of [(18)F]FMT PET in non-small-cell lung cancer (NSCLC) patients. Tumor uptake of [(18)F]FMT was compared with that of 2-[(18)F]-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and correlated with L-type amino acid transporter 1 (LAT1) expression.

Experimental design: Fifty NSCLC patients were enrolled in this study, and a pair of PET study with [(18)F]FMT and [(18)F]FDG was done. LAT1 expression and Ki-67 labeling index of the resected tumors were analyzed by immunohistochemical staining.

Results: For the primary tumor detection, [(18)F]FMT PET exhibited a sensitivity of 90% whereas the sensitivity for [(18)F]FDG PET was 94%. For lymph node staging, the sensitivity and specificity of [(18)F]FMT PET were 57.8% and 100%, and those of [(18)F]FDG PET were 65.7% and 91%, respectively. The expression of LAT1 in squamous cell carcinoma and large cell carcinoma was significantly higher than that in adenocarcinoma. [(18)F]FMT uptake was also higher in squamous cell carcinoma and large cell carcinoma than in adenocarcinoma. Uptake of [(18)F]FMT in the tumor is closely correlated with LAT1 expression (rho = 0.890).

Conclusion: [(18)F]FMT PET had no false-positives in the detection of primary tumor and lymph node metastasis and could improve the diagnostic performance in NSCLC. Uptake of [(18)F]FMT correlated with the expression of LAT1 that showed a significant association with cellular proliferation.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Carcinoma, Large Cell / diagnosis
  • Carcinoma, Large Cell / metabolism
  • Carcinoma, Large Cell / pathology
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • False Positive Reactions
  • Female
  • Fluorine Radioisotopes / pharmacology*
  • Humans
  • Immunohistochemistry / methods
  • Ki-67 Antigen / biosynthesis
  • Large Neutral Amino Acid-Transporter 1 / metabolism
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / pathology*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Staging / methods*
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / pharmacology*
  • Sensitivity and Specificity
  • Treatment Outcome

Substances

  • Fluorine Radioisotopes
  • Ki-67 Antigen
  • Large Neutral Amino Acid-Transporter 1
  • Radiopharmaceuticals