Fibroblast Activation Protein–Directed Imaging Outperforms 18F-FDG PET/CT in Malignant Mesothelioma: A Prospective, Single-Center, Observational Trial

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FIGURE 1.
Enrollment flowchart. IHC = immunohistochemistry.
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FIGURE 2.
Primary endpoint. (A) DAB immunohistochemical staining of FAP-α in pleural mesothelioma specimen and respective positive scores. No negative sample was reported in this cohort. (B) Spearman correlation shows moderate association between ⁶⁸Ga-FAPI46 PET uptake intensity and FAP immunohistochemistry score for available malignant pleural mesothelioma specimen (n = 18) (SUV_max: r = 0.49, P = 0.037; SUV_peak: r = 0.51, P = 0.030).
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FIGURE 3.
Male patient with suspected pleural mesothelioma before surgical biopsy. Ce-CT shows pleural mass and nodular thickening of left pleura with no morphologic signs of local nodal involvement (lymph nodes < 10 mm). ¹⁸F-FDG shows high circular uptake in pleura (SUV_max, 11.4) and additionally positive lymph nodes (SUV_max, 5.5) in levels 4 R/L, 5, 7, and 10 L (red arrows), whereas ⁶⁸Ga-FAPI46 shows only high uptake in pleura (SUV_max, 8.7). Thoracic lymph node levels are determined by International Associate for the Study of Lung Cancer. R = right; L = left. Endobronchial ultrasound–guided transbronchial fine-needle aspiration ruled out metastatic diseases of respective lymph node levels and revealed nodal anthracosis. MIP = maximum-intensity projection.

TABLE 1.

Patient Characteristics (n = 41)

Characteristic	Data
Age (y)
Mean ± SD	71.8 ± 8.6
Median	73.0
Range	49.0–87.0
Sex
Male	34 (82.9%)
Female	7 (17.1%)
Diagnosis
Malignant pleural mesothelioma	35 (85.4%)
Malignant peritoneal mesothelioma	2 (4.9%)
Benign	4 (9.7%)
Histologic subtype mesothelioma
Epitheloid	27 (72.9%)
Biphasic	4 (10.8%)
Sarcomatoid	4 (10.8%)
Pleomorphic	2 (5.4%)
UICC stage, initial
IA	2 (4.8%)
IB	14 (34.1%)
II	5 (12.2%)
III	1 (2.4%)
IV	10 (24.4%)
Not applicable/missing	9 (22.0%)
Cancer risk factors
Asbestosis/metal working	24 (58.5%)
Smoking	14 (34.1%)

TABLE 2.

Diagnostic Performance of ⁶⁸Ga-FAPI46 PET and ¹⁸F-FDG PET Compared with Confirmed Reference Validation

Basis	Modality	Reference	Sensitivity	Specificity	PPV	NPV	Accuracy
Per patient	⁶⁸Ga-FAPI46	Histopathology	100.0 (90.6–100.0)	25.0 (1.3–69.9)	92.5 (80.1–97.4)	100.0 (5.2–100.0)	92.7 (80.1–98.5)
	¹⁸F-FDG	Histopathology	97.3 (86.2–99.9)	50.0 (8.9–91.1)	94.7 (82.7–99.1)	66.7 (11.9–98.3)	92.3 (79.1–98.4)
Per region	⁶⁸Ga-FAPI46	Histopathology	98.0 (89.5–99.9)	81.1 (65.8–90.5)	87.5 (76.4–93.8)	96.8 (83.8–99.8)	90.8 (82.7–96.0)
		Composite standard	96.9 (89.5–99.5)	90.3 (81.3–95.2)	90.0 (81.0–95.1)	97.1 (89.8–99.5)	93.4 (87.9–97.0)
	¹⁸F-FDG	Histopathology	95.9 (86.3–99.3)	36.8 (23.4–52.7)	66.2 (54.6–76.1)	87.5 (64.0–97.8)	70.11 (59.4–79.5)

TABLE 3.

Detection Rates Compared for ⁶⁸Ga-FAPI46 vs. Ce-CT vs. ¹⁸F-FDG

	PET-positive results or CT lesions
Parameter	⁶⁸Ga-FAPI46	Ce-CT	¹⁸F-FDG	P (χ²)
Total lesions (n = 252)	144 (57.1)	128 (50.8)	219 (86.8)	0.0001
Per-patient basis (n = 41)	40 (97.6)	39 (95.1)	39 (95.1)	0.3
Per-region basis (n = 123)	69 (71.9)	79 (82.3)	87 (90.6)	0.06
Primary	40 (97.6)	39 (95.1)	38 (92.7)
Local nodal	13 (31.7)	21 (51.2)	27 (65.9)
Metastatic	16 (39.0)	19 (46.3)	22 (53.7)