Comparison of [68Ga]Ga-FAPI-04 and [18F]FDG PET/CT for detection of bone metastases of lung cancer

Abstract

Background: Bone metastases of lung cancer typically indicate disease progression and poor prognosis. Early and accurate detection is crucial for staging, treatment planning, and prognostic evaluation. This study aimed to compare the diagnostic value of gallium 68-labeled fibroblast-activation protein inhibitor-04 ([⁶⁸Ga]Ga-FAPI-04) and fluorine 18-labeled fluorodeoxyglucose ([¹⁸F]FDG) positron-emission tomography/computed tomography (PET/CT) imaging in detecting bone metastases in lung cancer.

Methods: A retrospective analysis was conducted on patients with pathologically confirmed lung cancer and clinically suspected bone metastases. These patients underwent both [⁶⁸Ga]Ga-FAPI-04 and [¹⁸F]FDG PET/CT imaging. Initially, all patient images were visually evaluated, and the diagnostic efficacy of the two imaging methods was compared at both the patient and lesion levels for detecting bone metastases from lung cancer. Additionally, a semi-quantitative analysis was performed to compare the optimal maximum standardized uptake value (SUVmax) threshold and diagnostic efficacy of the two examinations for diagnosing benign and malignant bone lesions.

Results: A total of 25 lung cancer patients were included in the study, with nine confirmed cases and 133 lesions of bone metastases. At the patient level, there were no statistically significant differences in the detection rate, sensitivity, specificity, positive predictive value, negative predictive value, or accuracy between [⁶⁸Ga]Ga-FAPI-04 and [¹⁸F]FDG PET/CT for identifying patients with bone metastases (P>0.05). At the lesion level, the detection rate, sensitivity, negative predictive value, and accuracy of [⁶⁸Ga]Ga-FAPI-04 PET/CT for detecting bone metastases were higher than those of [¹⁸F]FDG PET/CT (81.37% vs. 57.14%, 98.50% vs. 69.17%, 88.24% vs. 34.92%, 90.68% vs. 70.81%), with statistically significant differences (P<0.01). The SUVmax of malignant bone lesions on both [⁶⁸Ga]Ga-FAPI-04 and [¹⁸F]FDG PET/CT was significantly higher than those of benign bone lesions, with statistically significant differences (P<0.05). Moreover, the SUVmax of benign and malignant bone lesions on [⁶⁸Ga]Ga-FAPI-04 PET/CT was significantly higher than those on [¹⁸F]FDG PET/CT, with statistically significant differences (P<0.01). In [⁶⁸Ga]Ga-FAPI-04 and [¹⁸F]FDG PET/CT imaging, the area under the curves (AUCs) of SUVmax for diagnosing bone metastases were 0.856 and 0.724, respectively, with statistically significant differences (P<0.05); the optimal diagnostic thresholds were 5.38 and 3.77, respectively. The sensitivity, negative predictive value, and accuracy of SUVmax based on [⁶⁸Ga]Ga-FAPI-04 PET/CT for diagnosing lung cancer bone metastases were higher than those based on [¹⁸F]FDG PET/CT (80.45% vs. 65.26%, 46.49% vs. 23.26%, 81.25% vs. 67.29%), with statistically significant differences (P<0.05).

Conclusions: Compared to [¹⁸F]FDG PET/CT, [⁶⁸Ga]Ga-FAPI-04 PET/CT significantly improves the detection rate of lung cancer bone metastases at the lesion level. Additionally, [⁶⁸Ga]Ga-FAPI-04 PET/CT offers superior image contrast and higher SUVmax, which also contribute to improving the accuracy of lung cancer bone metastasis diagnosis. This allows for more accurate staging of patients, enabling precise individualized treatment and improving patient prognosis.

Keywords: Bone metastasis; computed tomography (CT); fibroblast-activation protein inhibitor (FAPI); fluorodeoxyglucose (FDG); positron-emission tomography (PET).

Figure 1

A 53-year-old female patient with invasive adenocarcinoma of the left upper lobe (early-stage lung cancer) had suffered a traffic accident injury 10 days prior. The [¹⁸F]FDG PET/CT scan accurately identified the compression fracture of the L4 vertebral body, whereas [⁶⁸Ga]Ga-FAPI-04 PET/CT demonstrated a false positive lesion. [⁶⁸Ga]Ga-FAPI-04 and [¹⁸F]FDG PET/CT images are shown. (A,C) MIP images with a pointed arrow indicating the primary lesion (a subsolid nodule with unremarkable FAPI and FDG uptake), and the dashed arrow indicates the fattening and wedge-shaped deformation of the L4 vertebral body. (B) [⁶⁸Ga]Ga-FAPI-04 PET/CT demonstrates flattening and wedge-shaped deformation of the L4 vertebral body, with increased FAPI expression (dashed arrow, SUVmax =7.33). (D) [¹⁸F]FDG PET/CT shows slightly increased glucose metabolism in the L4 vertebral body (dashed arrow, SUVmax =2.53). The patient recovered well after surgery and showed no abnormalities during follow-up. The final diagnosis was a compression fracture of the L4 vertebral body, rather than bone metastasis. [¹⁸F]FDG, fluorine 18-labeled fluorodeoxyglucose; [⁶⁸Ga]Ga-FAPI-04, gallium 68-labeled fibroblast-activation protein inhibitor-04; CT, computed tomography; FAPI, fibroblast-activation protein inhibitor; FDG, fluorodeoxyglucose; MIP, maximum intensity projection; PET, positron-emission tomography; SUVmax, maximum standardized uptake value.

Figure 2

A 66-year-old male patient with peripheral lung cancer (adenocarcinoma) in the upper lobe of the right lung. The [⁶⁸Ga]Ga-FAPI-04 and [¹⁸F]FDG PET/CT images are shown. (A,C) MIP images with a pointed arrow indicating the primary lesion, and the dashed arrows denote the degenerative osteophytes on the anterior edge of the T9/10 and T11/12 vertebral bodies. (B) [⁶⁸Ga]Ga-FAPI-04 PET/CT demonstrates degenerative osteophytes on the anterior edge of T9/10 and T11/12 vertebral bodies with increased FAPI expression (dashed arrows, SUVmax =3.6). (D) [¹⁸F]FDG PET/CT shows no significant increase in glucose metabolism in the corresponding areas (dashed arrows). The patient recovered well after surgery and showed no abnormalities during follow-up, leading to a final diagnosis of degenerative osteophytes. [¹⁸F]FDG, fluorine 18-labeled fluorodeoxyglucose; [⁶⁸Ga]Ga-FAPI-04, gallium 68-labeled fibroblast-activation protein inhibitor-04; CT, computed tomography; FAPI, fibroblast-activation protein inhibitor; FDG, fluorodeoxyglucose; MIP, maximum intensity projection; PET, positron-emission tomography; SUVmax, maximum standardized uptake value.

Figure 3

A 61-year-old male patient with centrally located lung cancer (squamous cell carcinoma) of the left lung accompanied by cervical lymph node metastasis. The [⁶⁸Ga]Ga-FAPI-04 PET/CT accurately identified bone metastases, whereas [¹⁸F]FDG PET/CT showed false negatives due to significant background interference around the left temporal bone lesion. [⁶⁸Ga]Ga-FAPI-04 and [¹⁸F]FDG PET/CT images are shown. (A,C) MIP images, where the solid arrows indicate the primary lesion, and the dashed arrows indicate inflammation around the left shoulder joint. (B) [⁶⁸Ga]Ga-FAPI-04 PET/CT demonstrates a slightly reduced local bone density and slightly elevated cortical bone in the left temporal bone, with a short diameter of 0.55cm and abnormally elevated FAPI expression (solid arrows, SUVmax =8.12). (D) [¹⁸F]FDG PET/CT shows significant background interference around the left temporal bone lesion, with no obvious abnormally increased glucose metabolism (solid arrows). The lesion was ultimately diagnosed as an osteolytic bone metastasis, which was confirmed by follow-up. [¹⁸F]FDG, fluorine 18-labeled fluorodeoxyglucose; [⁶⁸Ga]Ga-FAPI-04, gallium 68-labeled fibroblast-activation protein inhibitor-04; CT, computed tomography; FAPI, fibroblast-activation protein inhibitor; FDG, fluorodeoxyglucose; MIP, maximum intensity projection; PET, positron-emission tomography; SUVmax, maximum standardized uptake value.

Figure 4

A 46-year-old female patient with peripheral lung cancer (adenocarcinoma) in the upper lobe of the left lung accompanied by multiple bone metastases (involving the skull, multiple vertebral bodies of the spine, multiple ribs on both sides, and pelvic bones). The [⁶⁸Ga]Ga-FAPI-04 PET/CT accurately identified bone metastases, whereas [¹⁸F]FDG PET/CT showed false negatives due to slightly increased local glucose metabolism of the lesions. [⁶⁸Ga]Ga-FAPI-04 and [¹⁸F]FDG PET/CT images are shown. (A,C) MIP images with a pointed arrow indicating the primary lesion and solid arrows indicating newly detected lesions on [⁶⁸Ga]Ga-FAPI-04 PET/CT. (B) [⁶⁸Ga]Ga-FAPI-04 PET/CT demonstrates no significant bone destruction in the left iliac bone and left sacrum, but abnormally elevated FAPI expression (solid arrows, SUVmax =6.57). (D) [¹⁸F]FDG PET/CT shows slightly increased local glucose metabolism in the left iliac bone and left sacrum (solid arrows, SUVmax =4.15). The final diagnosis of this lesion was osteoblastic bone metastasis, which was confirmed through follow-up. [¹⁸F]FDG, fluorine 18-labeled fluorodeoxyglucose; [⁶⁸Ga]Ga-FAPI-04, gallium 68-labeled fibroblast-activation protein inhibitor-04; CT, computed tomography; FAPI, fibroblast-activation protein inhibitor; FDG, fluorodeoxyglucose; MIP, maximum intensity projection; PET, positron-emission tomography; SUVmax, maximum standardized uptake value.

Figure 5

A 57-year-old female patient with peripheral lung cancer (adenocarcinoma) in the middle lobe of the right lung, accompanied by multiple bone metastases (skull, multiple vertebral bodies of the spine, multiple ribs on both sides, pelvic bones, and limb bones), liver metastasis, and lymph node metastasis. The [⁶⁸Ga]Ga-FAPI-04 and [¹⁸F]FDG PET/CT images are presented. (A,E) MIP images with arrowheads indicating the primary lesion. Compared to [¹⁸F]FDG PET/CT, [⁶⁸Ga]Ga-FAPI-04 PET/CT showed significantly higher tracer uptake, better contrast, and detected more lesions. For instance, (B,F) [⁶⁸Ga]Ga-FAPI-04 PET/CT demonstrated no significant bone destruction in the occipital and left frontal bones, but abnormally increased FAPI expression (solid arrows, SUVmax =11.34). In contrast, [¹⁸F]FDG PET/CT showed high background interference around the left occipital and frontal bones without obvious abnormally increased glucose metabolism, leading to a final diagnosis of bone metastasis lesion with normal bone structure. (C,G) [⁶⁸Ga]Ga-FAPI-04 PET/CT revealed mixed bone destruction in the L2 vertebral body (short diameter of 3.41 cm) and no significant abnormality in bone density of the left 11^th rib at the axillary-dorsal segment. FAPI expression was abnormally increased in these lesions (solid arrows, SUVmax =26.63). On [¹⁸F]FDG PET/CT, glucose metabolism was slightly increased in the L2 vertebral lesion (solid arrows, SUVmax =4.31) but not significantly increased in the left 11^th rib at the axillary-dorsal segment. These lesions were diagnosed as mixed and normal bone structure metastasis lesions, respectively. (D,H) [⁶⁸Ga]Ga-FAPI-04 PET/CT showed decreased bone density in bilateral femoral necks and right ischial tuberosity, and increased bone density in the left ischial tuberosity. These lesions ranged from 0.53 to 2.05 cm in short diameter with abnormally increased FAPI expression (solid arrows, SUVmax =25.61). On [¹⁸F]FDG PET/CT, no significant abnormality in glucose metabolism was observed in the left ischial tuberosity, while other lesions showed slightly increased glucose metabolism (solid arrows, SUVmax =5.09). These lesions were diagnosed as osteolytic and osteoblastic bone metastatic tumors, which were confirmed by follow-up. [¹⁸F]FDG, fluorine 18-labeled fluorodeoxyglucose; [⁶⁸Ga]Ga-FAPI-04, gallium 68-labeled fibroblast-activation protein inhibitor-04; CT, computed tomography; FAPI, fibroblast-activation protein inhibitor; FDG, fluorodeoxyglucose; MIP, maximum intensity projection; PET, positron-emission tomography; SUVmax, maximum standardized uptake value.

Figure 6

Comparison of ROC curves for SUVmax in diagnosing bone metastases from lung cancer between [⁶⁸Ga]Ga-FAPI-04 and [¹⁸F]FDG PET/CT imagings. [¹⁸F]FDG, fluorine 18-labeled fluorodeoxyglucose; [⁶⁸Ga]Ga-FAPI-04, gallium 68-labeled fibroblast-activation protein inhibitor-04; AUC, area under the curve; CT, computed tomography; FAPI, fibroblast-activation protein inhibitor; FDG, fluorodeoxyglucose; PET, positron-emission tomography; ROC, receiver operating characteristic; SUVmax, maximum standardized uptake value.