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Relationship Between Tumor Immune Markers and Fluorine-18-α-Methyltyrosine ([18F]FAMT) Uptake in Patients with Lung Cancer

  • Kimihiro Shimizu
  • Kyoichi KairaEmail author
  • Tetsuya Higuchi
  • Takeshi Hisada
  • Takehiko Yokobori
  • Tetsunari Oyama
  • Takayuki Asao
  • Yoshito Tsushima
  • Ken Shirabe
Research Article
  • 18 Downloads

Abstract

Purpose

3-[18F]Fluoro-α-methyl-L-tyrosine ([18F]FAMT) is an amino acid positron emission tomography (PET) tracer specific for cancer detection by assessment of tumor amino acid metabolism. Little is known on whether or not the uptake of [18F]FAMT within cancer cells is associated with the expression of programmed death ligand-1 (PD-L1), a predictor of anti-PD-1 antibody efficacy. We conducted a clinicopathological study to assess the expression of PD-L1 and the presence of tumor-infiltrating lymphocytes (TILs) in patients with non-small cell lung cancer (NSCLC) diagnosed by PET.

Procedures

A total of 75 patients with NSCLC who underwent [18F]FAMT and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET were enrolled in the study. Tumor specimens were stained by immunohistochemistry for glucose transporter 1 (Glut1), PD-L1 (using different antibody clones including E1L3N and 28-8), CD3, CD4, and CD8. The uptake of [18F]FAMT was correlated with clinicopathological variables.

Results

High uptake of [18F]FAMT was significantly associated with disease staging, initial treatment (surgical resection or chemotherapy), and the expression of PD-L1 (E1L3N). The value of the maximum standardized uptake value (SUVmax) for [18F]FAMT was significantly correlated with PD-L1 (E1L3N) expression, Glut1, and the SUVmax for [18F]FDG in patients with histological results of adenocarcinoma (AC) and advanced disease. A validation cohort for anti-PD-L1 using clone 28-8 showed a statistically significant correlation between SUVmax for [18F]FAMT and the expression of PD-L1 (28-8) and between the expression of PD-L1 (E1L3N) and PD-L1 (28-8).

Conclusions

The uptake of [18F]FAMT on PET imaging was significantly correlated with PD-L1 expression in NSCLC, especially in patients with AC and advanced disease.

Key words

PD-L1 [18F]FAMT PET Amino acid metabolism Lung cancer Tumor immune markers 

Notes

Compliance with Ethical Standards

Conflict of Interest

KK has received research grants and a speaker honorarium from Boehringer Ingelheim Company, Ono Pharmaceutical Company, Bristol-Myers Company, and Chugai Pharmaceutical Company. All remaining authors have declared no conflicts of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© World Molecular Imaging Society 2019

Authors and Affiliations

  • Kimihiro Shimizu
    • 1
  • Kyoichi Kaira
    • 1
    • 2
    • 3
    Email author
  • Tetsuya Higuchi
    • 4
  • Takeshi Hisada
    • 5
  • Takehiko Yokobori
    • 2
  • Tetsunari Oyama
    • 6
  • Takayuki Asao
    • 7
  • Yoshito Tsushima
    • 4
  • Ken Shirabe
    • 1
  1. 1.Department of General Surgical ScienceGunma University, Graduate School of MedicineMaebashiJapan
  2. 2.Department of Innovative Immune-Oncology TherapeuticsGunma University, Graduate School of MedicineMaebashiJapan
  3. 3.Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical CenterSaitama University HospitalSaitamaJapan
  4. 4.Department of Diagnostic Radiology and Nuclear MedicineGunma University, Graduate School of MedicineMaebashiJapan
  5. 5.Department of Respiratory MedicineGunma University, Graduate School of MedicineMaebashiJapan
  6. 6.Department of Diagnostic PathologyGunma University, Graduate School of MedicineMaebashiJapan
  7. 7.Big Data Center for Integrative AnalysisGunma University Initiative for Advanced ResearchMaebashiJapan

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