Relationship Between Tumor Immune Markers and Fluorine-18-α-Methyltyrosine ([18F]FAMT) Uptake in Patients with Lung Cancer
- 18 Downloads
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.
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.
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).
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 wordsPD-L1 [18F]FAMT PET Amino acid metabolism Lung cancer Tumor immune markers
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.
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 was obtained from all individual participants included in the study.
- 3.Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, de Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC, KEYNOTE-189 Investigators (2018) Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 378:2078–2092CrossRefGoogle Scholar
- 4.Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O'Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L (2018) Nivolumab plus Ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med 378:2093–2104CrossRefGoogle Scholar
- 5.Kaira K, Higuchi T, Naruse I, Arisaka Y, Tokue A, Altan B, Suda S, Mogi A, Shimizu K, Sunaga N, Hisada T, Kitano S, Obinata H, Yokobori T, Mori K, Nishiyama M, Tsushima Y, Asao T (2018) Metabolic activity by 18F-FDG-PET/CT is predictive for early response after nivolumab in previously treated NSCLC. Eur J Nucl Med Mol Imaging 45:56–66CrossRefGoogle Scholar
- 11.Kaira K, Oriuchi N, Shimizu K, Ishikita T, Higuchi T, Imai H, Yanagitani N, Sunaga N, Hisada T, Ishizuka T, Kanai Y, Endou H, Nakajima T, Endo K, Mori M (2009) Evaluation of thoracic tumor with (18) F-FMT and (18) F-FDG PET-CT: a clinicopathological study. Int J Cancer 124:1152–1160CrossRefGoogle Scholar
- 15.Takada K, Toyokawa G, Okamoto T, Baba S, Kozuma Y, Matsubara T, Haratake N, Akamine T, Takamori S, Katsura M, Shoji F, Honda H, Oda Y, Maehara Y (2017) Metabolic characteristics of programmed cell death-ligand 1-expressing lung cancer on 18F-fluorodeoxyglucose positron emission tomography/computed tomography. Cancer Med 6:2552–2561CrossRefGoogle Scholar
- 23.Clark CA, Gupta HB, Sareddy G, Pandeswara S, Lao S, Yuan B, Drerup JM, Padron A, Conejo-Garcia J, Murthy K, Liu Y, Turk MJ, Thedieck K, Hurez V, Li R, Vadlamudi R, Curiel TJ (2016) Tumor-intrinsic PD-L1signals regulate cell growth, pathogenesis, and autophagy in ovarian cancer and melanoma. Cancer Res 76:6964–6974CrossRefGoogle Scholar
- 24.Kaira K, Oriuchi N, Otani Y, Shimizu K, Tanaka S, Imai H, Yanagitani N, Sunaga N, Hisada T, Ishizuka T, Dobashi K, Kanai Y, Endou H, Nakajima T, Endo K, Mori M (2007) Fluorine-18-alpha-methyltyrosine positron emission tomography for diagnosis and staging of lung cancer: a clinicopathologic study. Clin Cancer Res 13:6369–6378CrossRefGoogle Scholar
- 26.Hirsch FR, McElhinny A, Stanforth D, Ranger-Moore J, Jansson M, Kulangara K, Richardson W, Towne P, Hanks D, Vennapusa B, Mistry A, Kalamegham R, Averbuch S, Novotny J, Rubin E, Emancipator K, McCaffery I, Williams JA, Walker J, Longshore J, Tsao MS, Kerr KM (2017) PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol 12:208–222CrossRefGoogle Scholar