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

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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.

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Author information

Author notes

  1. Kimihiro Shimizu, Kyoichi Kaira, and Tetsuya Higuchi contributed equally to this article.

Authors and Affiliations

  1. Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan

    Kimihiro Shimizu, Kyoichi Kaira & Ken Shirabe

  2. Department of Innovative Immune-Oncology Therapeutics, Gunma University, Graduate School of Medicine, Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Kyoichi Kaira & Takehiko Yokobori

  3. Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama University Hospital, 1397-1 Yamane, Hidaka-City, Saitama, 350-1298, Japan

    Kyoichi Kaira

  4. Department of Diagnostic Radiology and Nuclear Medicine, Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan

    Tetsuya Higuchi & Yoshito Tsushima

  5. Department of Respiratory Medicine, Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan

    Takeshi Hisada

  6. Department of Diagnostic Pathology, Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan

    Tetsunari Oyama

  7. Big Data Center for Integrative Analysis, Gunma University Initiative for Advanced Research, Maebashi, Japan

    Takayuki Asao

Authors
  1. Kimihiro Shimizu
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Correspondence to Kyoichi Kaira.

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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.

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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.

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

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Shimizu, K., Kaira, K., Higuchi, T. et al. Relationship Between Tumor Immune Markers and Fluorine-18-α-Methyltyrosine ([18F]FAMT) Uptake in Patients with Lung Cancer. Mol Imaging Biol 22, 1078–1086 (2020). https://doi.org/10.1007/s11307-019-01456-w

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