Search

Supplementary Data

In recent years, quinoline-based fibroblast activation protein (FAP) inhibitors (FAPI) have shown promising results in the diagnosis of cancer and several other diseases, making them the hotspot of much productive research. This review summarizes the literature for the state-of-the-art FAPI-PET imaging for cancer diagnosis compared with fluorodeoxyglucose (FDG)-PET. We also summarize the use of FAPI-PET for therapeutic regimen improvement and fibroblast activation protein (FAP)-targeted molecule modification strategies, as well as preliminary clinical studies regarding FAP-targeted radionuclide therapy. Our qualitative summary of the literature to date can inform future research directions, medical guidelines, and optimal clinical decision-making.

Supplementary Data from A Paradigm of Cancer Immunotherapy Based on 2-[18F]FDG and Anti–PD-L1 mAb Combination to Enhance the Antitumor Effect

Purpose:Efforts have been devoted to select eligible candidates for PD-1/PD-L1 immune checkpoint blocker (ICB) immunotherapy. Here, we have a serendipitous finding of positron emission tomography (PET) imaging tracer 2-[18F]FDG as a potential immunomodulator. Therefore, we hypothesize that 2-[18F]FDG could induce PD-L1 expression change and create an immune-favorable microenvironment for tumor immunotherapy.Experimental Design:We designed a series of assays to verify PD-L1 upregulation, and tested immunotherapy regimens based on 2-[18F]FDG and anti–PD-L1 mAb, as monotherapy and in combination, in fully immunocompetent mice of MC38 and CT26 models. PD-L1 expression and tumor microenvironment (TME) changes were analyzed by Western blot, transcriptomics study, and flow-cytometric analysis.Results:PD-L1 was upregulated in a time- and dose-dependent manner after being induced by 2-[18F]FDG. The activation of NF-κB/IRF3 pathway and STAT1/3-IRF1 pathway play crucial parts in modulating PD-L1 expression after DNA damage and repair. Improved αPD-L1 mAb utilization rate and significant tumor growth delay were observed when the personalized therapeutic alliance of 2-[18F]FDG stimulation and ICB was used. In addition, combination of 2-[18F]FDG with αPD-L1 mAb could reprogram a TME from “cold” to “hot,” to make low immunoactivity tumors sensitive to ICB therapy.Conclusions:In summary, this promising paradigm has the potential to expand the traditional tumor theranostics. 2-[18F]FDG-based ICB immunotherapy is highly significant in enhancing antitumor effect. A research of 2-[18F]FDG-based ICB immunotherapy has been proposed to enhance the antitumor effect.

Purpose Radiopharmaceuticals targeting fibroblast activation protein alpha (FAP) are increasingly studied for diagnostic and therapeutic applications. We discovered FAP expression at immunohistochemistry (IHC) in the alpha cells of the Langerhans insulae of few patients. Therefore, we planned an investigation aimed at describing FAP expression in the pancreas and discussing the implications for radioligand applications. Methods We retrospectively included 40 patients from 2 institutions (20 pts each) according to the following inclusion/exclusion criteria: i) pathology proven pancreatic ductal adenocarcinoma and neuroendocrine tumors (NET), 10 pts per each group at each center; ii) and availability of paraffin-embedded tissue and iii) clinical-pathological records. We performed IHC analysis and applied a semiquantitative visual scoring system (0, negative staining; 1, present in less than 30%; 2, present in more than 30% of the area). FAP expression was assessed according to histology – NET(n = 20) vs ductal adenocarcinoma(n = 20) - and to previous treatments within the adenocarcinoma group. Local ethics committee approved the study (No. INT 21/16, 28 January 2016). Results The population consisted of 24 males, 16 females, median age 68, range (14–84) years; 8/20 adenocarcinoma patients received chemotherapy. In all the Langerhans insulae (40/40) pancreatic alpha cells were found to express FAP, with a score of 2. No difference was found among NET(20/20) and adenocarcinoma(20/20); nor according to neoadjuvant chemotherapy in the adenocarcinoma cohort (received or not received). Conclusion Pancreatic Langerhans islets alpha cells normally express FAP. This is not expected to influence the diagnostic accuracy of FAP-targeting tracers. In the therapeutic setting, our results suggest the need to better elucidate FAPI radioligands’ effects on the Langerhans insulae function.

Background and purpose: Quickly screening of high-risk of peptic ulcer (PU) is of great significance to avoid gastrointestinal bleeding after antiplatelet therapy. In this study, we hoped to find a fast and less invasive method for PU screening. Methods: The clinical data of health examined population who were admitted for taking gastroscopic assessment in our hospital, from January 2019 to June 2020, was prospectively collected. PU was defined as a gastric or duodenal mucosal defect >5mm in diameter on gastroscopic assessment. Results: A total of 902 blood samples were enrolled into analysis. Blood indices showed that PGI and albumin (ALB) were both independently associated with PU (all PPPConclusion: Both serum PGI and ALB were associated with the increased rate of PU in health examined population, and the PACS score based on these two items may be used to identify the population with high risk of PU.

Streptococcus pneumoniae (S. pneumoniae) is one of the most common community-associated pathogens responsible for pneumonia in children. This retrospective study aimed to investigate the molecular characteristics of S. pneumoniae isolated from children with community-acquired pneumonia (CAP) under 5 years in Chengdu, China. Molecular characteristics of S. pneumoniae included serotype and virulence factor performed by using PCR method and sequence types (STs) determined by sequencing seven housekeeping genes. In addition, the potential relationships between molecular characteristics were depicted by minimum spanning tree and correspondence analysis. The prevailing serotypes were 19F (18.52%), 6B (17.59%), 19A (13.89%), 6A (6.48%) and 23F (5.56%) among 108 isolates. The overall coverage rates of 7-valent, 10-valent, 13-valent, 15-valent and 20-valent pneumococcal conjugate vaccines (PCVs) were 47.32, 48.1, 75, 75 and 78.7%, respectively. Meanwhile, the coverage rates of PCV13 among the isolates from CAP patients aged 23F‐1, Spain6B‐2, Taiwan19F‐14, Netherlands3‐31 and Denmark14‐32. Additionally, most of the isolates carried ply, psaA, nanA, pavA, piaA and CC271 isolates expressed more of nanA than non-CC271 isolates. Moreover, there were strong relevant relationships among STs, serotypes and virulence factors. Considering serotypes and virulence factors together can be used as the foundation for the formulation of vaccine strategy.

Purpose To evaluate the diagnostic accuracy and clinical impact of gallium-68-labelled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI) PET/CT in primary and metastatic breast cancer and compare the results with those of standard-of-care imaging (SCI) and [18F]Fluorodeoxyglucose (FDG) PET/CT. Methods Patients with diagnosed or suspected breast cancer who underwent concomitant [68Ga] Ga-FAPI (FAPI-46) and [18F]FDG PET/CT scans from October 2019 to March 2022 were retrospectively analysed. Breast ultrasound (US) imaging was performed in all treatment-naïve patients as SCI. The maximum standard uptake value (SUVmax), tumour-to-background ratio (TBR), lesion detection rate, and tumour-node-metastasis (TNM) classifications between [68Ga]Ga-FAPI and [18F]FDG PET/CT were evaluated, and compared. Results Twenty-eight women (median age, 52.5 y; range, 28–80 y) were included. Among them, 5 patients underwent evaluation for a definitive diagnosis of suspected breast lesions, 9 underwent initial staging, and 14 were evaluated for the detection of recurrence. The sensitivities of breast US, [18F]FDG, and [68Ga]Ga-FAPI PET/CT for detecting primary breast tumours were 80%, 70%, and 100%, respectively. Regarding the diagnosis of recurrent/metastatic lesions, the per-lesion detection rate of [68Ga]Ga- FAPI PET/CT was significantly higher than that of [18F]FDG, which including local and regional recurrence (128 vs. 88), neck lymph node (LN) metastases (33 vs. 15), abdomen LN metastases (28 vs. 3), bone metastases (146 vs. 59), and liver metastases (28 vs. 11). Compared with [18F]FDG, [68Ga]Ga-FAPI PET/CT upstaged five patients’ TNM staging/re-staging (7/27, 26%) and changed five patients’ clinical management (5/27, 19%). Compared to SCI, [68Ga]Ga-FAPI upstaged ten patients' TNM staging/re-staging (9/27, 33%) and changed the therapeutic regimen of seven patients (7/27, 26%). There was no significant association between FAPI-derived SUVmax and receptor status/histologic type in both primary and metastatic lesions. Conclusion [68Ga]Ga-FAPI PET/CT was superior to [18F]FDG in diagnosing primary and metastatic breast cancer, with higher radiotracer uptake and TBR, especially in the detection of primary/recurrent tumour, abdominal LN metastases, liver, and bone metastases. [68Ga]Ga-FAPI PET/CT is superior to [18F]FDG and SCI in TNM staging and may improve tumour staging, recurrence detection, and implementation of necessary treatment modifications.

Cancer-associated fibroblasts (CAFs) are crucial components of the tumor microenvironment. Fibroblast activation protein (FAP) is overexpressed in CAFs. FAP-targeted molecular imaging agents, including FAP inhibitor (FAPI)-04 and FAPI-46, have shown promising results in tumor diagnosis. However, these molecules have relatively short tumor-retention time for peptide-targeted radionuclide therapy applications. We aimed to design a 68Ga-labeled FAPI dimer (denoted as 68Ga-DOTA-2P(FAPI)2) to optimize the pharmacokinetics and evaluate whether this form is more effective than its monomeric analogs. Methods:68Ga-DOTA-2P(FAPI)2 was synthesized based on the quinoline-based FAPI variants (FAPI-46), and its binding properties were assayed in CAFs. Preclinical pharmacokinetics was determined in FAP-positive patient-derived xenografts (PDXs) using small-animal PET and biodistribution experiments. The effective dosimetry of 68Ga-DOTA-2P(FAPI)2 was evaluated in three healthy volunteers, and PET/ CT imaging of 68Ga-FAPI-46 and 68Ga-DOTA-2P(FAPI)2 was performed in three cancer patients. Results:68Ga-DOTA-2P(FAPI)2 was stable in phosphate-buffered saline and fetal bovine serum for 4 h. The FAPI dimer showed high affinity and specificity for FAP in-vitro and in-vivo. The tumor uptake of 68Ga-DOTA-2P(FAPI)2 was approximately two-fold stronger than that of 68Ga-FAPI-46 in PDXs, while the healthy organs showed low tracer uptake and fast body clearance. The effective dose of 68Ga-DOTA-2P(FAPI)2 was 1.19E-02 mSv/MBq, calculated using OLINDA. Finally, PET/CT scans in three cancer patients revealed higher intratumoral uptake of 68Ga-DOTA-2P(FAPI)2 than that of 68Ga-FAPI-46 in all tumor lesions (maximum standardized uptake value: 8.1-39.0 vs. 1.7-24.0, respectively; P < 0.001). Conclusion:68Ga-DOTA-2P(FAPI)2 has increased tumor uptake and retention properties compared to 68Ga-FAPI-46, and it could be a promising tracer for both diagnostic imaging and targeted therapy of malignant tumors with positive expression of FAP.

Background and purpose To compare 68Ga-fibroblast activation protein inhibitor (FAPI) and 18F-FDG PET/CT in imaging locally advanced oesophageal cancer, and evaluate the potential usefulness of 68Ga-FAPI PET/CT on gross target volume (GTV) delineation aimed at radiotherapy planning for oesophageal cancer as compared with contrast-enhanced CT (CE-CT) and 18F-FDG PET/CT. Materials and methods Twenty-one patients with newly diagnosed oesophageal cancer who underwent both 18F-FDG and 68Ga-FAPI PET/CT scans were selected. GTVs of the primary tumours based on CE-CT (GTVCT), PET/CT, and CE-CT plus PET/CT were delineated. Gross tumour lengths were measured by GTVs and endoscopy and recorded. Results The 68Ga-FAPI PET showed significantly higher radiotracer uptake than 18F-FDG PET (median SUVmax 16.71 vs. 11.23; P = 0.002) in the primary tumours. SUV thresholds of FAPI ×20%, 30%, 40%, and FDG ×40% showed similar lesion lengths compared with that in endoscopic examination (P > 0.05). GTVCT demonstrated the largest volume (median: 48.80 mm3, range: 14.83–162.23 mm3) than PET-based GTVs. For PET/CT-guided complementary contouring of GTVCT, four patients (19%) were increased by FAPI ×20% and 30%, two patients (9.5%) were increased by FAPI ×40%, and only one patient was increased by FDG ×40%. Furthermore, the volume of GTV based on CE-CT plus FAPI ×20%, 30%, and 40% showed no significant difference with GTVCT and planning target volume based CE-CT plus FAPI-PET and meets the organ at risk standard. Conclusion The 68Ga-FAPI PET/CT methodology showed favourable tumour-to-background contrast in oesophageal cancer and might provide additional information for target volume delineation and help avoid tumour geographic misses.

Background Accurate clinical staging is crucial to managing gastrointestinal cancer, but fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT has limitations. Targeting fibroblast-activation protein is a newer diagnostic approach for the visualization of tumor stroma, and gallium 68 (68Ga)-labeled fibroblast-activation protein inhibitors (FAPIs), hereafter 68Ga-FAPIs, present a promising alternative to 18F-FDG. Purpose To compare the diagnostic efficacy of 68Ga-FAPI PET/CT in primary and metastatic lesions of gastrointestinal malignancies with that of 18F-FDG PET/CT. Materials and Methods Images from patients with gastric, duodenal, and colorectal cancers who underwent contemporaneous 18F-FDG and 68Ga-FAPI PET/CT between October 2019 through June 2020 were retrospectively analyzed. 18F-FDG and 68Ga-FAPI uptakes were compared by using the Wilcoxon signed-rank test. The McNemar test was used to compare the diagnostic performance between the two techniques. Results Thirty-five patients (median age, 64 years [interquartile range, 53-68 years]; 18 men) were evaluated. In treatment-naive patients (n = 19), 68Ga-FAPI PET/CT led to upstaging of the clinical TNM stage in four (21%) patients compared with 18F-FDG PET/CT. Tracer uptake was higher with 68Ga-FAPI PET/CT than with 18F-FDG PET/CT in primary lesions (gastric cancer: 12.7 vs 3.7, respectively, P = .003; colorectal cancer: 15.9 vs 7.9, P = .03), involved lymph nodes (6.7 vs 2.4, P < .001), and bone and visceral metastases (liver metastases: 9.7 vs 5.2, P < .001; peritoneal metastases: 8.4 vs 3.6, P < .001; bone metastases: 4.3 vs 2.2, P < .001; lung metastases: 4.4 vs 1.9, P = .01). In addition, the sensitivity of 68Ga-FAPI PET/CT was higher than that of 18F-FDG PET/CT in the detection of primary tumors (100% [19 of 19] vs 53% [10 of 19], respectively; P = .004), lymph nodes (79% [22 of 28] vs 54% [15 of 28], P < .001), and bone and visceral metastases (89% [31 of 35] vs 57% [20 of 35], P < .001). Conclusion Gallium 68 fibroblast-activation protein inhibitor PET/CT was superior to fluorine 18 fluorodeoxyglucose PET/CT in the detection of primary and metastatic lesions in gastric, duodenal, and colorectal cancers, with higher tracer uptake in most primary and metastatic lesions. Published under a CC BY 4.0 license.

PET imaging targeting fibroblast activation protein (FAP) on the surface of cancer-associated fibroblasts has yielded promising tumor diagnostic results. FAP-2286 contains cyclic peptides as FAP-binding motifs to optimize tumor retention compared with the small molecule FAP inhibitor (FAPI) series (FAPI-04/46). The aim of this study was to evaluate the diagnostic accuracy of the

Background: Streptococcus pneumoniae (S. Pneumoniae) is one of the most common community-associated pathogens responsible for pneumonia in children. This retrospective study aimed to investigate the molecular characteristics of S. Pneumoniae isolated from children with community-acquired pneumonia (CAP) under 5 years in Chengdu, China. Methods: Molecular characteristics of S. Pneumoniae included serotype and virulence factor performed by using PCR method and sequence types (STs) determined by sequencing seven housekeeping genes. In addition, the potential relationships between molecular characteristics were depicted by minimum spanning tree and correspondence analysis.Results: The prevailing serotypes were 19F (18.52%), 6B (17.59%), 19A (13.89%), 6A (6.48%) and 23F (5.56%) among 108 isolates. The overall coverage rates of 7-valent, 10-valent, 13-valent pneumococcal conjugate vaccines (PCVs) were 47.32%, 48.1%, 75%, respectively. Meanwhile, the coverage rates of PCV13 among the isolates from CAP patients aged ply, psaA, nanA, pavA, piaA, and CC271 isolates expressed more of nanA than non-CC271 isolates. Moreover, there were strong relevant relationships among STs, serotypes, virulence factors.Conclusion: Considering serotypes and virulence factors together can be used as the foundation for the formulation of vaccine strategy.

Purpose: Efforts have been devoted to select eligible candidates for PD-1/PD-L1 immune checkpoint blocker (ICB) immunotherapy. Here, we have a serendipitous finding of positron emission tomography (PET) imaging tracer 2-[18F]FDG as a potential immunomodulator. Therefore, we hypothesize that 2-[18F]FDG could induce PD-L1 expression change and create an immune-favorable microenvironment for tumor immunotherapy. Experimental Design: We designed a series of assays to verify PD-L1 upregulation, and tested immunotherapy regimens based on 2-[18F]FDG and anti–PD-L1 mAb, as monotherapy and in combination, in fully immunocompetent mice of MC38 and CT26 models. PD-L1 expression and tumor microenvironment (TME) changes were analyzed by Western blot, transcriptomics study, and flow-cytometric analysis. Results: PD-L1 was upregulated in a time- and dose-dependent manner after being induced by 2-[18F]FDG. The activation of NF-κB/IRF3 pathway and STAT1/3-IRF1 pathway play crucial parts in modulating PD-L1 expression after DNA damage and repair. Improved αPD-L1 mAb utilization rate and significant tumor growth delay were observed when the personalized therapeutic alliance of 2-[18F]FDG stimulation and ICB was used. In addition, combination of 2-[18F]FDG with αPD-L1 mAb could reprogram a TME from “cold” to “hot,” to make low immunoactivity tumors sensitive to ICB therapy. Conclusions: In summary, this promising paradigm has the potential to expand the traditional tumor theranostics. 2-[18F]FDG-based ICB immunotherapy is highly significant in enhancing antitumor effect. A research of 2-[18F]FDG-based ICB immunotherapy has been proposed to enhance the antitumor effect.

Cancer-associated fibroblasts (CAFs) are crucial components of the tumor microenvironment. Fibroblast activation protein (FAP) is overexpressed in CAFs. FAP-targeted molecular imaging agents, including the FAP inhibitors (FAPIs) 04 and 46, have shown promising results in tumor diagnosis. However, these molecules have a relatively short tumor-retention time for peptide-targeted radionuclide therapy applications. We aimed to design a

Purpose To analyze the mismatch repair (MMR) status and PD-L1 expression in nasopharyngeal carcinoma (NPC), and investigate whether PD-L1 and MMR status could be used as a biomarker for predicting response of immune checkpoint blockades (ICBs) treatment. Patients and methods A total of 108 patients were initially histopathologically diagnosed with NPC between December 2017 and September 2018. All tissue specimens were collected before any treatment. Tumor tissue MMR status was determined by both immunohistochemistry and PCR. The expression of PD-L1 in NPC tissue was analyzed immunohistochemically. High PD-L1 expression in tumor cells (TC) or tumor-infiltrating immune cells (TIIC) was defined as ≥50% of corresponding cells with membranous staining. Results Tissue samples were obtained from 102 patients after written informed consent was obtained. Seventy-one (69.6%) patients were treated in our hospital after diagnosis. Disease in stages I-III accounted for 35 (49.3%) cases, while stage IVa-IVb was identified in 36 (50.7%) cases. Only two of 102 patients were identified as MMR-deficient (dMMR) by IHC and PCR. High PD-L1 expression in TC was confirmed in 77 of the 102 (75.5%) NPC cases, while only 13 of the 102 (12.7%) NPC cases were considered to exhibit high PD-L1 expression in TIIC. PD-L1 expression in TC was positively correlated with T stage (P=0.033), while PD-L1 expression in TIIC was negatively associated with plasma Epstein-Barr virus DNA load (P=0.021), N stage (P=0.009), M stage (P=0.014), and clinical stage (P=0.001). Conclusion dMMR is a rare event in NPC and may not be a prospective biomarker to predict the effectiveness of treatment with ICBs in clinical practice. It was also determined that high PD-L1 expression in NPC is quite common and the importance of distinguishing PD-L1 expression in TC and TIIC was highlighted.

Rationale: Radiotherapy combined with immunotherapy has revealed promising outcomes in both preclinical studies and ongoing clinical trials. Targeted radionuclide therapy (TRT) is a branch of radiotherapy concerned with the use of radioisotopes, radiolabeled molecules or nanoparticles that deliver particulate radiation to cancer cells. TRT is a promising approach in cases of metastatic disease where conventional treatments are no longer effective. The increasing use of TRT raises the question of how to best integrate TRT with immunotherapy. In this study, we proposed a novel therapeutic regimen that combined programmed death ligand 1 (PD-L1)-based immunotherapy with peptide-based TRT (177Lu as the radionuclide) in the murine colon cancer model. Methods: To explore the most appropriate timing of immunotherapy after radionuclide therapy, the anti-PD-L1 antibody (αPD-L1 mAb) was delivered in a concurrent or sequential manner when 177Lu TRT was given. Results: The results demonstrated that TRT led to an acute increase in PD-L1 expression on T cells, and TRT in combination with αPD-L1 mAb stimulated the infiltration of CD8+ T cells, which improved local tumor control, overall survival and protection against tumor rechallenge. Moreover, our data revealed that the time window for this combination therapy may be critical to outcome. Conclusions: This therapeutic combination may be a promising approach to treating metastatic tumors in which TRT can be used. Clinical translation of the result would suggest that concurrent rather than sequential blockade of the PD-1/PD-L1 axis combined with TRT improves overall survival and long-term tumor control.

Background: Neuropilin-1 (NRP-1) and integrin αvβ3 receptors are both overexpressed in breast cancer. Methods: We developed and synthesized a heterodimeric tracer consisting of Arg−Gly−Asp (RGD) and Ala-Thr-Trp-Leu-Pro-Pro-Arg (ATWLPPR) peptides that simultaneously targets integrin αvβ3 and NRP-1. We then investigated the diagnostic efficacy of RGD-ATWLPPR heterodimeric peptides in MCF-7 xenograft models in mice. DOTA-conjugated RGD-ATWLPPR peptides were then radiolabeled with 68Ga, and the receptor-binding characteristics and tumor-targeting efficacy of 68Ga-DOTA-RGD-ATWLPPR were investigated in vitro and in vivo. We also detected integrin αvβ3 and NRP-1 expression in MCF-7 cells and tumor tissues. Results: The peptide showed high stability in vitro. Static PET/CT imaging studies showed that MCF-7 tumors were clearly visible 30 min and 60 min after 68Ga-DOTA-RGD-ATWLPPR injection. Further, the heterodimer showed higher tumor uptake than 68Ga-DOTA-RGD or 68Ga-DOTA-ATWLPPR alone. High specificity was shown in blocking studies using RGD and ATWLPPR peptides. MicroPET/CT and biodistribution studies using 68Ga-DOTA-RGD-ATWLPPR showed that the tracer specifically targets NRP-1 and integrin ανβ3 receptors. Conclusions: Compared with 68Ga-DOTA-RGD and 68Ga-DOTA-ATWLPPR, 68Ga-DOTA-RGD-ATWLPPR has higher binding affinity, better targeting efficiency, and longer tumor retention time. It therefore has potential as an imaging probe for breast cancer detection.

Efforts have been devoted to select eligible candidates for PD-1/PD-L1 immune checkpoint blocker (ICB) immunotherapy based on radiopharmaceuticals. Here, we have observed a tracking-to-triggering (referred to as “T2T”) immunoediting effect of the employed radionuclides. In particular, we found the usefulness of 2-[18F]FDG in cancer ICB therapy. Given that the PD-L1 expression is upregulated after the administration of various radiotracers, the predictive result from PET/SPECT imaging should be treated with caution. Viewed positively, radiotracers are potential immunomodulators to create an immune-favorable microenvironment for tumor immunotherapy. Improving αPD-L1 mAb utilization and significant tumor growth delay are observed when the personalized therapeutic alliance of radiotracer stimulation and ICB are employed. This new paradigm has the potential to expand the traditional tumor theranostic model and implement precision cancer immunotherapy.

ObjectiveProgrammed death-ligand 1 (PD-L1) expression status is a crucial index for identifying patients who will benefit from anti-programmed cell death protein 1 (PD-1)/PD-L1 therapy for non-small cell lung cancer (NSCLC). However, the concordance of Tumor Proportion Score (TPS) between biopsies and matched surgical specimens remains controversial. This study aims to evaluate the concordance of PD-L1 expression between image-guided percutaneous biopsies and matched surgical specimens.MethodWe evaluated 157 patients diagnosed with operable NSCLC on both surgical tissue sections and matched lung biopsies retrospectively. The patients underwent either regular computed tomography (CT)-guided biopsy (n = 82) or positron emission tomography (PET)/CT-guided biopsy (n = 75). The concordance between surgical specimens and lung biopsies for PD-L1 TPS was evaluated using Cohen’s kappa (κ) coefficient.ResultsImmunohistochemical expression of PD-L1 was evaluated in both surgical resected specimens and matched biopsies in the eligible 138 patients. The concordance rate of PD-L1 expression between surgical tissue sections and matched biopsies was fairly high at 84.1% (116/138), and the κ value was 0.73 (95% CI: 0.63–0.83, P < 0.001). The concordance rate was higher for tissue sections from PET/CT-guided biopsy than for tissue sections from CT-guided biopsy [88.6% (62/70, κ value: 0.81) vs 79.4% (54/68, κ value: 0.66)].ConclusionPD-L1 TPS was strongly concordant between surgical specimens and matched lung biopsies. Thus, the routine evaluation of PD-L1 expression in diagnostic percutaneous biopsies could be reliable for identifying patients who will benefit from anti-PD-1/PD-L1 immunotherapy.