Fibroblast activation Protein-Targeted PET/CT using [18 F]FAP-2286 for the evaluation of lung cancer: A comparative study with [18 F]FDG PET/CT

Abstract

Purpose: FAP-2286, which is a novel cyclic peptide that targets fibroblast activation protein (FAP), demonstrates enhanced plasma stability and improved receptor selectivity compared with small-molecule FAP inhibitors (FAPIs). Although [18 F]FAP-2286 exhibits benefits due to the favorable characteristics of fluorine-18-labeled tracers, its diagnostic performance in lung cancer remains to be fully elucidated. This study aimed to compare the diagnostic efficacy of [18 F]FAP-2286 PET/CT with that of [18 F]FDG PET/CT in lung cancer patients.

Methods: Thirty patients with suspected lung cancer (18 men and 12 women; median age: 64 years [IQR: 35-81]) underwent both [18 F]FAP-2286 and [18 F]FDG PET/CT for initial staging (n = 27) or the detection of recurrence (n = 3). Diagnostic performance was assessed using histopathology and clinical follow-up as reference standards. The quantitative analysis included the maximum standardized uptake value (SUV_max) and target-to-background ratio (TBR).

Results: Compared with [18 F]FDG, [18 F]FAP-2286 PET/CT significantly increased the TBR in primary tumors (11.60 ± 6.02 vs. 5.80 ± 3.08; P < 0.001), whereas the SUV_max was not significantly different (15.20 ± 8.25 vs. 13.81 ± 7.73; P = 0.524). Although [18 F]FAP-2286 PET/CT demonstrated a lower detection rate for metastatic lymph nodes (67.46% [85/126] vs. 86.51% [109/126]; P < 0.001), it exhibited a higher true positive rate (95.29% vs. 68.81%; P < 0.001). For distant metastases, [18 F]FAP-2286 PET/CT demonstrated superior detection of bone (98.80% vs. 72.46%) and brain lesions (100% vs. 72.73%).

Conclusion: Compared with [18 F]FDG, [18 F]FAP-2286 PET/CT demonstrates superior performance for detecting bone metastases and provides more accurate N and M staging. These findings suggest that [18 F]FAP-2286 PET/CT may serve as a valuable alternative for the comprehensive evaluation of lung cancer patients.

Fig. 1

Study flowchart

Fig. 2

Biodistribution analysis between the fatty meal group and the non-fatty meal group. PET-based biodistribution analysis of [18 F]FAP-2286 and [18 F]FDG in normal organs at 1 h after injection. The gallbladder of patient (A) exhibited obvious visualization on [18 F]FAP-2286 images with no intake of fatty meals. Patient (B) ate a fatty meal before PET/CT imaging, and there was no significant uptake of FAP-2286 agents in the gallbladder. However, the uptake of fat by lung lesions was not affected, regardless of whether a fatty meal was consumed. The results are presented as the means and SDs from 26 patients (C)

Fig. 3

SUV_max and TBR of [18 F]FAP-2286 and [18 F]FDG PET/CT in pulmonary tumors, positive lesions, positive lymph nodes and bone metastases. [18 F]FAP-2286 PET/CT accumulation was significantly greater than [18 F]FDG accumulation with respect to the SUV_max regarding the positive lymph nodes (*, P = 0.010) and bone metastases (*, P = 0.012), as well as the TBR in terms of pulmonary tumors (***, P = 0.000), positive lesions (***, P = 0.000), positive lymph nodes (***, P = 0.000), bone metastases (***, P = 0.000), brain metastases (***, P = 0.000) and pleura metastases (**, P = 0.004)

Fig. 4

Images of a 42-year-old woman with newly diagnosed lung adenocarcinoma for tumor staging. [18 F]FAP-2286 (A-E) is highly expressed in multiple lymph nodes (red arrow, SUV_max: 22.8) and bones (red arrow, SUV_max: 16.6). [18 F]FDG (F-J) demonstrates uptake in the lymph nodes (red arrow, SUV_max: 5.2) and bones (red arrow, SUV_max: 4.3). Compared with [18 F]FDG PET/CT, more metabolic lesions were identified on the [18 F]FAP-2286 image

Fig. 5

Images of a 68-year-old man with newly diagnosed lung cancer for tumor staging. [18 F]FAP-2286 (A-D) uptake is observed in the bilateral ribs, right ilium and left scapula (red arrow, SUV_max: 6.7). [18 F]FDG PET/CT (E-H) reveals uptake in the lower right ribs (red arrow, SUV_max: 1.6) but no uptake in the ilium or scapula

Fig. 6

A 61-year-old woman with metastatic lung adenosquamous carcinoma underwent cancer restaging imaging. [18 F]FAP-2286 demonstrates many lesions in brain metastases (A, red arrows, SUV_max: 5.7), and [18 F]FDG demonstrates FDG uptake in brain metastases (C, red arrows, SUV_max: 56.7). The lesions appear as an uneven density of brain tissue on CT images (B). The TBRs of [18 F]FAP-2286 and [18 F]FDG were 28.41 and 3.81, respectively. [18 F]FAP-2286 PET/CT image depicts another positive lesion with focal uptake of the tracer in the cerebral falx region (A, blue arrow, SUV_max: 1.5, TBR: 7.5), which was negative on the [18 F]FDGPET/CT images (C, blue arrow)

Fig. 7

Bar graph and table showing a comparison of [18 F]FAP-2286 and [18 F]FDG PET/CT for lung cancer TNM staging, T staging, N staging, and M staging

Fig. 8

Images of a 73-year-old man with lung adenocarcinoma. Primary lung cancer (size: 2.3 cm×1.4 cm) in the upper lobe of the right lung was detected with intense uptake of [18 F]FAP-2286 and [18 F]FDG (maximum standardized uptake values: 7.8 and 4.0, respectively) (A, E). [18 F]FDG PET/CT (E-H) demonstrates lymph node uptake in the mediastinum (red arrow, SUV_max: 10.7) and bilateral hilum of (blue arrow, SUV_max: 12.9) and relatively low uptake on [18 F]FAP-2286 images (A-D, red arrow, SUV_max: 1.6, blue arrow, SUV_max: 4.3). The mediastinal blood pool SUV of [18 F]FDG and [18 F]FAP-2286 was 2.4 and 1.7, respectively. The patient subsequently underwent resection of the upper lobe of the right lung and lymph node sampling surgery. Pathology revealed that the right lung mass was adenocarcinoma and that the lymph nodes were hyperplastic. The results suggest the possibility of false positives in the diagnosis of lymph nodes on [18 F]FDG