Initial Evaluation of [18F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions

Abstract

The ¹⁸F-labeled fibroblast activation protein inhibitor (FAPI) [¹⁸F]FAPI-74 has the benefit of a higher synthetic yield and better image resolution than ⁶⁸Ga-labeled FAPI. We preliminarily evaluated the diagnostic performance of [¹⁸F]FAPI-74 PET in patients with various histopathologically confirmed cancers or suspected malignancies. Methods: We enrolled 31 patients (17 men and 14 women) with lung cancer (n = 7), breast cancer (n = 5), gastric cancer (n = 5), pancreatic cancer (n = 3), other cancers (n = 5), and benign tumors (n = 6). Twenty-seven of the 31 patients were treatment-naïve or preoperative, whereas recurrence was suspected in the remaining 4 patients. Histopathologic confirmation was obtained for the primary lesions of 29 of the 31 patients. In the remaining 2 patients, the final diagnosis was based on the clinical course. [¹⁸F]FAPI-74 PET scanning was performed 60 min after the intravenous injection of [¹⁸F]FAPI-74 (240 ± 31 MBq). The [¹⁸F]FAPI-74 PET images were compared between the primary or local recurrent lesions of malignant tumors (n = 21) and nonmalignant lesions (n = 8: type-B1 thymomas, granuloma, solitary fibrous tumor, and postoperative or posttherapeutic changes). The uptake and number of detected lesions on [¹⁸F]FAPI-74 PET were also compared with those on [¹⁸F]FDG PET for available patients (n = 19). Results: [¹⁸F]FAPI-74 PET showed higher uptake in primary lesions of various cancers than in nonmalignant lesions (median SUV_max, 9.39 [range, 1.83-25.28] vs. 3.49 [range, 2.21-15.58]; P = 0.053), but some of the nonmalignant lesions showed high uptake. [¹⁸F]FAPI-74 PET also showed significantly higher uptake than [¹⁸F]FDG PET (median SUV_max, 9.44 [range, 2.50-25.28] vs. 5.45 [range, 1.22-15.06] in primary lesions [P = 0.010], 8.86 [range, 3.51-23.33] vs. 3.84 [range, 1.01-9.75] in lymph node metastases [P = 0.002], and 6.39 [range, 0.55-12.78] vs. 1.88 [range, 0.73-8.35] in other metastases [P = 0.046], respectively). In 6 patients, [¹⁸F]FAPI-74 PET detected more metastatic lesions than [¹⁸F]FDG PET. Conclusion: [¹⁸F]FAPI-74 PET showed higher uptake and detection rates in primary and metastatic lesions than did [¹⁸F]FDG PET. [¹⁸F]FAPI-74 PET is a promising novel diagnostic modality for various tumors, especially for precise staging before treatment, including characterization of tumor lesions before surgery. Moreover, ¹⁸F-labeled FAPI ligand might serve a higher demand in clinical care in the future.

Keywords: PET; [18F]FAPI-74; cancer-associated fibroblast; fibroblast activation protein; oncology.

Graphical abstract

FIGURE 1.

Comparison of uptake on [¹⁸F]FAPI-74 PET between malignant tumors and nonmalignant lesions: SUV_max (A) and T/N ratio (B) (with P value by Mann–Whitney U test).

FIGURE 2.

Comparison of uptake between [¹⁸F]FAPI-74 PET and [¹⁸F]FDG PET: SUV_max in primary lesions, LN metastases, and other metastases (A) and number of detected metastatic lesions on [¹⁸F]FAPI-74 PET compared with [¹⁸F]FDG PET (B) (with P value by Wilcoxon signed-rank test).

FIGURE 3.

A 68-y-old man with multiple LN and peritoneal metastases of pancreatic cancer. (A) Comparison of maximum-intensity projection images: image on right shows fusion with positive lesions on [¹⁸F]FAPI-74 PET (red area) and [¹⁸F]FDG PET (blue area). (B) PET/CT images on [¹⁸F]FAPI-74 PET and [¹⁸F]FDG PET (arrows indicate metastatic lesions). [¹⁸F]FAPI-74 PET detected more metastatic lesions than [¹⁸F]FDG PET (SUV_max of primary lesion is 9.4 and 3.2, respectively). Brain uptake is decreased on [¹⁸F]FDG PET because of high blood glucose level (277 mg/dL).

FIGURE 4.

A 59-y-old woman with multiple LN metastases of breast cancer. (A) Comparison of maximum-intensity projection images: image on right shows fusion with positive lesions on [¹⁸F]FAPI-74 PET (red area) and [¹⁸F]FDG PET (blue area), (B) PET/CT images on [¹⁸F]FAPI-74 PET and [¹⁸F]FDG PET (arrows indicate metastatic lesions). [¹⁸F]FAPI-74 PET detected more metastatic lesions than [¹⁸F]FDG PET (SUV_max of primary lesion is 19.6 and 13.0, respectively).

FIGURE 5.

Comparison of PET/CT images on [¹⁸F]FAPI-74 PET and [¹⁸F]FDG PET of 80-y-old man with lung adenocarcinoma with ground-glass opacity (arrows indicate primary lesions). [¹⁸F]FAPI-74 PET showed clearer uptake than [¹⁸F]FDG PET (SUV_max of primary lesion is 2.5 and 1.2, respectively).