Abstract
PurposeHeterogeneity is found in the tumor microenvironment among different pathological types of tumors. Radionuclide-labeled fibroblast-activation-protein inhibitor (FAPI), as an important tracer for non-invasive imaging of the tumor microenvironment, can be used to evaluate the expression of FAP in cancer-associated fibroblasts, macrophages, and tumor cells. Our aim was to explore the ability of [18F]AlF-NOTA-FAPI-04 positron emission tomography (PET)/computed tomography (CT) to distinguish different types of lung cancer by evaluating the uptake of this tracer in primary and metastatic lesions.MethodsWe prospectively enrolled 61 patients with histopathologically proven primary lung cancer with metastases. PET/CT scanning was performed before any antitumor therapy and 1 h after injection of 235.10 ± 3.89 MBq of [18F]AlF-NOTA-FAPI-04. Maximum standard uptake values (SUVmax) were calculated for comparison among primary and metastatic lesions. Immunohistochemical staining for FAP was performed on tumor specimens.ResultsSixty-one patients with adenocarcinoma (ADC, n = 30), squamous cell carcinoma (SCC, n = 17), and small cell lung cancer (SCLC, n = 14) were enrolled in this study, and 61 primary tumors and 199 metastases were evaluated. No difference in [18F]AlF-NOTA-FAPI-04 uptake was observed among primary ADC, SCC, and SCLC tumors (P = 0.198). Additionally, no difference in uptake was found between primary and metastatic lesions of lung cancer with the same pathological type (P > 0.05). However, uptake did differ among metastases of differing pathological types (P < 0.001). The SUVmax of metastatic lymph nodes was highest for SCC, followed by ADC and then SCLC (P < 0.001). The SUVmax of bone metastases also was highest for SCC, followed by ADC and SCLC (P < 0.05), but no difference was observed between ADC and SCLC. The SUVmax of metastases in other organs was higher in SCC cases than in ADC cases but did not differ between SCC and SCLC or ADC and SCLC. Bone metastases exhibited higher uptake than those of lymph nodes and other organs in SCC and ADC (P < 0.05) but not in SCLC. Positive correlations were found between FAPI uptake and FAP expression in surgical plus biopsy specimens (r = 0.439, P = 0.012) and surgical specimens (r = 0.938, P = 0.005).Conclusion[18F]AlF-NOTA-FAPI-04 PET/CT imaging revealed differences in FAP expression in metastases of lung cancer, with the highest expression specifically in bone metastases, and thus, may be valuable for distinguishing different pathological types of lung cancer.
Highlights
Lung cancer is the most commonly diagnosed and deadliest cancer worldwide
This prospective study was approved by the local ethics committee of Shandong Cancer Hospital and NOTA-fibroblast-activation-protein inhibitor (FAPI)-04 was radiolabeled with 18F according to the following procedure: 2–10 GBq 18F fluoride produced by medical cyclotron (MINITRACE Cyclotron, GE, USA) was trapped on an anion exchange cartridge (Waters Plus QMA Light Cartridge, preconditioned with 5 mL saline and 10 mL water) and eluted with 0.30 mL saline
[18F]AlF-NOTA-FAPI-04 uptake values in primary and metastatic lesions were comparable in patients with the same pathological type of lung cancer (Fig. 3b, c, d, and Fig. 4)
Summary
About 40% of cases are diagnosed at an advanced stage, and the 5-year survival rate of patients with advanced lung cancer is less than 10% [1, 2]. FAP expression has been reported on the surface of tumor stromal cells, macrophages, and tumor cells [5]. It is highly expressed in more than 90% of epithelial tumors [6] but expressed at low levels in physiological conditions [7, 8]. For this reason, it is often used as a marker of pro-tumorigenic stroma [9]. The coevolution and continuous participation of the stroma and tumor cells in the process of tumorigenesis are the main reasons for the heterogeneity of the tumor microenvironment
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