2-Deoxy-2-[fluorine-18] fluoro-d-glucose uptake on positron emission tomography is associated with programmed death ligand-1 expression in patients with pulmonary adenocarcinoma

Kaira, Kyoichi; Shimizu, Kimihiro; Kitahara, Shinsuke; Yajima, Toshiki; Abe, Jun; Kosaka, Takayuki; Ohtaki, Yoichi; Higuchi, Tetsuya; Oyama, Tetsunari; Asao, Takayuki; Mogi, Akira

doi:10.1016/j.ejca.2018.06.022

Cited by 81 publications

(78 citation statements)

References 19 publications

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“…The mechanism of FDG uptake within tumor cells is concerned with the presence of glucose metabolism, hypoxia, and angiogenesis [9][10][11]. The level of PD-L1 expression is associated with Glut1 and HIF-1α in patients with NSCLC [12,13]. Therefore, some studies attempt to search whether baseline 18 F-FDG PET-CT can provide useful information on the expression of checkpoint inhibitors in patients with NSCLC, in order to distinguish patients from the potential for prolonged benefits.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, some studies attempt to search whether baseline 18 F-FDG PET-CT can provide useful information on the expression of checkpoint inhibitors in patients with NSCLC, in order to distinguish patients from the potential for prolonged benefits. Indeed, there is a statistically significant association between tumor metabolic parameters on 18 F-FDG PET-CT and PD1/PD-L1 expression in resected tumor specimens [12][13][14]25]. Grizzi et al [26] found that almost all patients (n = 27) with SUV max ≤ 17.1 or SUV mean ≤ 8.3 on baseline PET had fast progression after 8 weeks immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism of FDG uptake within tumor cells is concerned with the presence of glucose metabolism, hypoxia, and angiogenesis [9][10][11]. The level of PD-L1 expression has been associated with that of glucose transporter 1 (Glut1) and hypoxia-inducible factor 1α (HIF-1α) in patients with NSCLC [12,13]. Lopci et al [14] found a direct association between SUV max and SUV mean with the expression of PD-1 (rho = 0.33; p = 0.017 and rho = 0.36; p = 0.009, respectively) in patients with NSCLC.…”

Section: Introductionmentioning

confidence: 99%

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The efficiency of 18F-FDG PET-CT for predicting the major pathologic response to the neoadjuvant PD-1 blockade in resectable non-small cell lung cancer

Tao

et al. 2020

Eur J Nucl Med Mol Imaging

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Purpose Investigate whether 18 F-FDG PET-CT has the potential to predict the major pathologic response (MPR) to neoadjuvant sintilimab in resectable NSCLC patients, and the potential of sifting patients who probably benefit from immunotherapy. Methods Treatment-naive patients with resectable NSCLC (stage IA-IIIB) received two cycles of sintilimab (200 mg, intravenously, day 1 and 22). Surgery was performed between day 29 and 43. PET-CT was obtained at baseline and prior to surgery. The following lean body mass-corrected metabolic parameters were calculated by PET VCAR: SUL max , SUL peak , MTV, TLG, ΔSUL max %, ΔSUL peak %, ΔMTV%, ΔTLG%. PET responses were classified using PERCIST. The above metabolic information on FDG-PET was correlated with the surgical pathology. (Registration Number: ChiCTR-OIC-17013726).Results Thirty-six patients received 2 doses of sintilimab, all of whom underwent PET-CT twice and had radical resection (35) or biopsy (1). MPR occurred in 13 of 36 resected tumors (36.1%, 13/36). The degree of pathological regression was positively correlated with SUL max (p = 0.036) of scan-1, and was negatively correlated with all metabolic parameters of scan-2, and the percentage changes of the metabolic parameters after neoadjuvant therapy (p < 0.05). According to PERCIST, 13 patients (36.1%, 13/36) showed partial metabolic response (PMR), 21 (58.3%, 21/36) had stable metabolic disease, and 2 (5.6%, 2/36) had progressive metabolic disease (PMD). There was a significant correlation between the pathological response and the PET responses which were classified using PERCIST. All (100.0%) the PMR (ΔSUL peak % < − 30.0%) tumors showed MPR. Conclusions 18 F-FDG PET-CT can predict MPR to neoadjuvant sintilimab in resectable non-small cell lung cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The efficiency of 18F-FDG PET-CT for predicting the major pathologic response to the neoadjuvant PD-1 blockade in resectable non-small cell lung cancer

Tao

et al. 2020

Eur J Nucl Med Mol Imaging

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“…Overexpression of glucose transporter 1 (GLUT1) is reported to be significantly correlated with 18 F‐FDG uptake in human cancers 24 . Recent studies have shown that PD‐L1 expression in tumor cells is closely correlated with the uptake of 18 F‐FDG and GLUT1 expression in patients with non–small‐cell lung cancer 25,26 . Heiden et al 27 used genome‐wide expression analyses and demonstrated that esophageal adenocarcinoma tumors with high FDG uptake are significantly associated with PD‐L1 expression.…”

Section: Introductionmentioning

confidence: 99%

Uptake of positron emission tomography tracers reflects the tumor immune status in esophageal squamous cell carcinoma

et al. 2020

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The relationship between the local immune status and cancer metabolism regarding 18F‐FDG and 18F‐FAMT uptake in esophageal squamous cell carcinoma (ESCC) remains unknown. The present study examined the correlations between tumor immune status, clinicopathological factors, and positron emission tomography (PET) tracer uptake in ESCC. Forty‐one ESCC patients who underwent 18F‐FDG PET and 18F‐FAMT PET before surgery were enrolled in the study. Immunohistochemistry was conducted for programmed death 1 (PD‐1), CD8, Ki‐67, CD34, GLUT1 (18F‐FDG transporter) and LAT1 (18F‐FAMT transporter). ESCC specimens with high tumoral PD‐L1 and high CD8‐positive lymphocytes were considered to have “hot tumor immune status.” High PD‐L1 expression (53.7%) was significantly associated with tumor/lymphatic/venous invasion (P = 0.028, 0.032 and 0.018), stage (P = 0.041), CD8‐positive lymphocytes (P < 0.001), GLUT1 (P < 0.001), LAT1 expression (P = 0.006), Ki‐67 labelling index (P = 0.009) and CD34‐positive vessel counts (P < 0.001). SUVmax of 18F‐FDG was significantly higher in high PD‐L1 cases than in low PD‐L1 cases (P = 0.009). SUVmax of 18F‐FAMT was significantly higher in high PD‐L1 (P < 0.001), high CD8 (P = 0.012) and hot tumor groups (P = 0.028) than in other groups. High SUVmax of 18F‐FAMT (≥4.15) was identified as the only predictor of hot tumor immune status. High PET tracer uptake was significantly associated with cancer aggressiveness and hot tumor immune status in ESCC. PET imaging may be an effective tool to predict tumor immune status in ESCC with respect to immune checkpoint inhibitor sensitivity.

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“…Effectively, PD-L1 promotes glycolytic metabolism in tumor cells, while this glucose consumption by tumors metabolically restricts T cells, notably by dampening their glycolytic capacity [17]. As a result, PD-L1 protein expression was significantly correlated to glucose transporter 1 (GLUT1) expression, which is the transporter of 18 F-FDG, in lung adenocarcinoma [18,19] and squamous-cell carcinoma [20]. In a meta-analysis about lung cancer including three studies (718 patients), 18 F-FDG PET SUVmax (maximal standardized uptake value reflecting tumor activity) and PD-L1 expression were slightly correlated (Spearman's correlation 0.36 (95% CI: 0.22; 0.50)), although this low value does not allow the SUVmax to be used as a replacement for the PDL1 status in lung cancer [21].…”

Section: F-fdg Pet/ctmentioning

confidence: 99%

Immunotherapy by Immune Checkpoint Inhibitors and Nuclear Medicine Imaging: Current and Future Applications

Decazes

Bohn

2020

Cancers

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Immunotherapy by using immune checkpoint inhibitors is a revolutionary development in oncology. Medical imaging is also impacted by this new therapy, particularly nuclear medicine imaging (also called radionuclide imaging), which uses radioactive tracers to visualize metabolic functions. Our aim was to review the current applications of nuclear medicine imaging in immunotherapy, along with their limitations, and the perspectives offered by this imaging modality. Method: Articles describing the use of radionuclide imaging in immunotherapy were researched using PubMed by April 2019 and analyzed. Results: More than 5000 articles were analyzed, and nearly 100 of them were retained. Radionuclide imaging, notably 18F-FDG PET/CT, already has a major role in many cancers for pre-therapeutic and therapeutic evaluation, diagnoses of adverse effects, called immune-related adverse events (IrAE), and end-of-treatment evaluations. However, these current applications can be hindered by immunotherapy, notably due to atypical response patterns such as pseudoprogression, which is defined as an increase in the size of lesions, or the visualization of new lesions, followed by a response, and hyperprogression, which is an accelerated tumor growth rate after starting treatment. To overcome these difficulties, new opportunities are offered, particularly therapeutic evaluation criteria adapted to immunotherapy and immuno-PET allowing us to predict responses to immunotherapy. Moreover, some new technological solutions are also promising, such as radiomic analyses and body composition on associated anatomical images. However, more research has to be done, notably for the diagnosis of hyperprogression and pseudoprogression. Conclusion: Immunotherapy, by its major impact on cancer and by the new patterns generated on images, is revolutionary in the field of medical images. Nuclear medicine imaging is already established and will be able to help meet new challenges through its plasticity.

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2-Deoxy-2-[fluorine-18] fluoro-d-glucose uptake on positron emission tomography is associated with programmed death ligand-1 expression in patients with pulmonary adenocarcinoma

Cited by 81 publications

References 19 publications

The efficiency of 18F-FDG PET-CT for predicting the major pathologic response to the neoadjuvant PD-1 blockade in resectable non-small cell lung cancer

The efficiency of 18F-FDG PET-CT for predicting the major pathologic response to the neoadjuvant PD-1 blockade in resectable non-small cell lung cancer

Uptake of positron emission tomography tracers reflects the tumor immune status in esophageal squamous cell carcinoma

Immunotherapy by Immune Checkpoint Inhibitors and Nuclear Medicine Imaging: Current and Future Applications

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