Generally, this study enrolled 28 cases (13 male, 15 female; median age: 60.5 years, range: 34-78 years). The basic features of these cases are detailed in Table 1.
The patients had been newly diagnosed with NSCLC, including 24 patients diagnosed with adenocarcinomas and 5 diagnosed with squamous cell carcinomas, with one patient (patient 17) having been simultaneously diagnosed with two primary tumors. In total, 16 patients underwent surgical resection, with 10 having simultaneously undergone mediastinal lymph node dissection. The remaining 12 patients underwent non-surgical antitumor treatment. Genetic testing was performed for 6 patients, of whom 3 were found to harbor tumors with epidermal growth factor receptor (EGFR) mutations, while 3 harbored wild-type adenocarcinomas.
Table 1 Basic patient characteristics
NO.
|
Sex
|
Age
|
Pathology
|
Primary tumor
site
|
Metastases site
|
TMN
|
1
|
F
|
44
|
ADC
|
right upper lobe
|
LNM; LM; PM
|
T4N2M1a
|
2
|
M
|
61
|
ADC
|
left upper lobe
|
LNM; AM
|
T1N3M1b
|
3
|
M
|
66
|
ADC
|
right upper lobe
|
None
|
T1N0M0
|
4
|
F
|
46
|
ADC
|
left upper lobe
|
LNM; BM
|
T1N3M1c
|
5
|
F
|
48
|
SCC
|
left lower lobe
|
None
|
T2N0M0
|
6
|
F
|
57
|
ADC
|
left lower lobe
|
LNM; HM; BM
|
T2N3M1c
|
7
|
F
|
53
|
ADC
|
left upper lobe
|
None
|
T1N0M0
|
8
|
F
|
72
|
ADC
|
right upper lobe
|
None
|
T1N0M0
|
9
|
M
|
70
|
ADC
|
right upper lobe
|
None
|
T1N0M0
|
10
|
F
|
78
|
ADC
|
left lower lobe
|
LM; PM; BM
|
T4N0M1b
|
11
|
M
|
68
|
ADC
|
left upper lobe
|
LNM
|
T1N2M0
|
12
|
F
|
57
|
ADC
|
right middle lobe
|
LNM
|
T1N3M0
|
13
|
M
|
69
|
SCC
|
right lower lobe
|
None
|
T2N0M0
|
14
|
M
|
49
|
ADC
|
right upper/ lower lobe
|
LNM, Pancreas, Kidney
|
T4N3M1c
|
15
|
F
|
46
|
ADC
|
right middle lobe
|
LNM
|
T2N3M0
|
16
|
M
|
63
|
ADC
|
left lower lobe
|
BM
|
T2N0M1c
|
17
|
F
|
68
|
ADC
ADC
|
right lower lobe
right middle lobe
|
LNM
|
T2N2M0
|
18
|
M
|
63
|
ADC
|
left upper lobe
|
LNM;HM; BM
|
T1N3M1c
|
19
|
M
|
71
|
SCC
|
right upper lobe
|
LNM; BM
|
T2N3M1b
|
20
|
M
|
67
|
SCC
|
right upper lobe
|
AM
|
T1N0M1b
|
21
|
M
|
34
|
ADC
|
right lower lobe
|
LNM; BM
|
T4N3M1c
|
22
|
F
|
58
|
ADC
|
right lower lobe
|
LNM; PM
|
T2N3M1a
|
23
|
F
|
61
|
ADC
|
left upper lobe
|
LNM
|
T2N1M0
|
24
|
F
|
60
|
ADC
|
right upper lobe
|
None
|
T2N0M0
|
25
|
M
|
56
|
SCC
|
left lower lobe
|
LNM
|
T3N2M0
|
26
|
F
|
45
|
ADC
|
right middle lobe
|
None
|
T1N0M0
|
27
|
F
|
53
|
ADC
|
right upper lobe
|
None
|
T1N0M0
|
28
|
M
|
68
|
ADC
|
right upper lobe
|
None
|
T1N0M0
|
SCC = squamous cell carcinoma; ADC = adenocarcinoma; LNM = lymph node metastasis; LM = lung metastasis; PM = Pleural metastasis; AM = adrenal metastasis; BM = bone metastasis; HM = hepatic metastases
|
Adverse event
No patients developed any adverse events, discomfort, or abnormalities with respect to heart rate, body temperature, blood pressure, or mental status within 2 h following imaging agent injection.
Comparison of visual assessment outcomes
Upon visual assessment, [68Ga]Ga-FAPI PET/CT enabled clearer metastatic and primary tumor visualization as compared to [18F]FDG PET/CT in a majority of patients. Specifically, [68Ga]Ga-FAPI outperformed [18F]FDG PET/CT for the visual evaluation of primary tumors (14/28 [50.0%] vs. 9/28 [32.1%]), lymph node metastases (9/15 [60.0%] vs. 5/15 [33.3%]), pleural metastases (3/3 [100.0%] vs. 0/3 [0%]), hepatic metastases (2/2 [100.0%] vs. 0/2 [0%]), and bone metastases (6/7 [85.7%] vs. 0/7 [0%]), but it performed less effectively for pulmonary (0/2 [0%] vs. 2/2 [100.0%]) and adrenal metastases (0/2 [0%] vs. 2/2 [100.0%]) (Fig 1).
Patient-based detection rate comparison
The primary tumor detection rates for [68Ga]Ga-FAPI and [18F]FDG PET/CT were similar in patient-based analyses (96.4% [27/28] vs. 92.9% [26/28]), as were the rates of detection for lymph node (93.3% [14/15] vs. 93.3% [14/15]), pulmonary (100% [2/2] vs. 100% [2/2]), pleural (100% [3/3] vs. 100% [3/3]), hepatic (100% [2/2] vs. 50% [1/2]), and bone metastases (100% [7/7] vs. 85.7% [6/7]). [68Ga]Ga-FAPI was discovered to be inferior to [18F]FDG PET/CT when used to detect adrenal metastases, however (0% [0/2] vs. 100% [2/2]) (Table 2).
Lesion-based detection rates
[68Ga]Ga-FAPI outperformed [18F]FDG PET/CT in a lesion-based analysis when detecting hepatic (100% [4/4] vs. 25% [1/4]) and bone metastases (97.6% [41/42] vs. 83.3% [35/42]), whereas [68Ga]Ga-FAPI was inferior to [18F]FDG PET/CT when utilized to detect adrenal metastases (0% [0/2] vs. 100% [2/2]). Both approaches performed similarly when used to detect primary tumors (96.6% [28/29] vs. 93.1% [27/29]), as well as lymph node (93.0% [53/57] vs. 86.0% [49/57]), pulmonary (100% [3/3] vs. 100% [3/3]), and pleural metastases (100% [8/8] vs. 87.5% [7/8]) (Table 2).
Table 2 Comparison of [68Ga]Ga-FAPI and [18F]FDG PET/CT semi-quantitative imaging parameters
Parameter
|
Imaging method
|
primary
tumor
|
Lymph node
metastasis
|
Lung
metastasis
|
Pleural
metastasis
|
Hepatic
metastasis
|
Adrenal
metastasis
|
Bone
metastasis
|
Patient-based analysis
|
|
28
|
15
|
2
|
3
|
2
|
2
|
7
|
No. of patients
|
68Ga-FAPI
|
27
|
14
|
2
|
3
|
2
|
0
|
7
|
18F-FDG
|
26
|
14
|
2
|
3
|
1
|
2
|
6
|
P
|
0.553
|
1.000
|
1.000
|
1.000
|
1.000
|
0.046
|
0.299
|
Lesion-based analysis
|
|
29
|
57
|
3
|
8
|
4
|
2
|
42
|
No. of lesions
|
68Ga-FAPI
|
28
|
53
|
3
|
8
|
4
|
0
|
41
|
18F-FDG
|
27
|
49
|
3
|
7
|
1
|
2
|
35
|
P
|
0.554
|
0.222
|
1.000
|
0.302
|
0.028
|
0.046
|
0.026
|
SUVmax
|
68Ga-FAPI
|
9.3 ± 4.6
|
8.4 ± 4.3
|
2.4 ± 1.6
|
10.8 ± 3.6
|
6.2 ± 2.1
|
1.2 ± 0.4
|
11.2 ± 5.5
|
18F-FDG
|
9.9 ± 6.9
|
6.4 ± 4.7
|
2.9 ± 1.9
|
5.5 ± 3.0
|
3.4 ± 0.27
|
6.4 ± 3.3
|
6.5 ± 3.9
|
P
|
0.631
|
0.003
|
0.192
|
<0.001
|
0.062
|
0.237
|
<0.001
|
TBR
|
68Ga-FAPI
|
26.3 ± 18.8
|
10.6 ± 6.3
|
3.4 ± 1.8
|
9.1 ± 2.8
|
11.4 ± 5.3
|
1.6 ± 0.1
|
16.2 ± 11.2
|
18F-FDG
|
24.0 ± 21.6
|
6.1 ± 4.9
|
4.8 ± 3.2
|
6.2 ± 3.3
|
1.3 ± 0.3
|
3.3 ± 2.5
|
5.9 ± 5.8
|
P
|
0.589
|
<0.001
|
0.215
|
0.001
|
0.027
|
0.500
|
<0.001
|
Quantitative analysis of [68Ga]Ga-FAPI and [18F]FDG PET/CT metabolic imaging parameters
The SUVmax and TBR values for [18F]FDG PET/CT and [68Ga]Ga-FAPI did not differ significantly when used for detecting primary tumors, pulmonary metastases, and adrenal metastases, while the SUVmax and TBR of [68Ga]Ga-FAPI were substantially superior to those for [18F]FDG PET/CT when used to discern lymph node, pleural, and bone metastases. When the SUVmax for these two imaging modalities did not differ significantly in the detection of hepatic metastases (P = 0.062), [68Ga]Ga-FAPI was correlated with a remarkably greater TBR value relative to that for [18F]FDG (P = 0.027) (Table 2).
The relationship between lesion length and SUVmax values
Significant correlations between lesion length and [68Ga]Ga-FAPI SUVmax values were noted for primary tumors, lymph node metastases, and bone metastases in Spearman’s correlation analyses, while [18F]FDG SUVmax values were only correlated with lesion length for primary tumors and lymph node metastases but not for bone metastases (Fig 2).
Prediction of EGFR mutation status
For six patients with lung adenocarcinoma who underwent genetic testing, the metabolic parameters (SUVmax, TBR) of two imaging modalities were lower in EGFR mutant than wild-type lung adenocarcinoma, although neither was significantly different (Fig 3).
N and M staging
Overall, 10 NSCLC cases in the current researh cohort underwent mediastinal lymph node dissection (patients 5, 8, 11, 17, 20, 23, 24, 26, 27, and 28). While 19 FDG-positive lymph nodes were found to be benign upon biopsy, just 4 FAPI-positive lymph nodes were confirmed to be benign. For these patients, [18F]FDG PET/CT and [68Ga]Ga-FAPI PET/CT results were consistent with N staging in 8 and 5 patients, respectively. [68Ga]Ga-FAPI PET/CT imaging led to a lower N-stage in 1 patient (patient 11) owing to overlooked lymph node metastases and a higher N-stage in 1 patient (patient 28) owing to the detection of additional false-positive lymph nodes. In contrast, [18F]FDG PET/CT detected additional false-positive lymph nodes in 5 patients (patients 11, 20, 23, 27, and 28) resulting in higher N staging for these individuals. Overall, NSCLC patient N-staging based upon [68Ga]Ga-FAPI results was more accurate than [18F]FDG PET/CT results for these same patients (80% [8/10] vs. 50% [5/10]).
Of the contributors considered in the present research, 12 (42.9%) exhibited distant metastatic lesions, while 16 (57.1%) did not. [68Ga]Ga-FAPI PET/CT enabled the accurate M-staging of 26 of these patients, while its failure to detect adrenal metastases results in a decreased M stage in 2 individuals (patients 2 and 20). [18F]FDG PET/CT enabled the accurate M-staging of 25 patients, with incorrect results in the remaining patients owing to 1 instance of false-positive adrenal modules (patient 13) and 2 instances of false-negative bone metastases (patients 16 and 21). The overall M-staging accuracy of [68Ga]Ga-FAPI PET/CT was superior to that of [18F]FDG PET/CT (92.9% [26/28] vs. 89.3% [25/28]).