Thirty-one patients successively diagnosed with suspected pancreatic malignancy by radiologic examinations (contrast-enhanced CT or MRI) were recruited in this study. Patients who were subjected to invasive examinations prior to PET scans, including histopathological biopsy, endoscopic retrograde cholangiopancreatography (ERCP), and stent placement; received adjuvant radiotherapy or chemotherapy before PET scans; or without available complete clinical or pathological records were excluded. The enrolled patients were subjected to both 68Ga-FAPI PET/MR as well as 18F-FDG PET/CT scans within one week. Prior to their inclusion in this study, all patients signed written informed consents.
Biological and clinical data, including sex, clinical presentation, age, and laboratory indexes were collected from each patient. Final diagnosis was based on the histopathological assessments of tumor samples harvested by surgical resection or biopsy. This prospective study was permitted by the Ethical Committee of the First Affiliated Hospital of Naval Medical University (Changhai Hospital, CHEC2021-071).
Synthesis and labeling of 68Ga-FAPI was according to a previously documented method . 68Ga was obtained from an in-house 68Ge-to-68Ga generator (ITG, Germany). Chelation was done after the adjustment of pH using sodium acetate. Then, for 10 min, heating of the reaction mixture was done to 100 °C for 10 min. The reactions integrity was assessed by radio-liquid chromatography. Solid-phase extraction of 68Ga compounds was performed before injection. The final product was sterile and pyrogen-free.
18F-FDG injections were obtained from Shanghai Atom Kexing Pharmaceutical Co., Ltd. (their radiochemical purity was> 95%).
68Ga-FAPI PET/MR imaging
PET/MR assessments were conducted on an integrated PET/MR scanner (Biograph mMR; Siemens Healthcare, Erlangen, Germany) that has a combination of PET and 3.0-T MRI scanners. Intravenous injection activity of 68Ga-FAPI was 1.85–3.70 MBq/kg. After a fast and simple MRI scout imaging sequence, a PET scan was conducted for the whole-body from the skull vertex to mid-thigh, in 5–6 bed positions. MRI was concurrently conducted using the protocol: T1-weighted 3D volumetric interpolated breath-hold examination (VIBE) with Dixon fat saturation (T1-VIBE-DIXON) (3D, transversal, TR 4.07 ms, TE 1.28 ms, flip angle 12°, 72 slices, 3 mm slice thickness, field of view (FOV) 400 × 400, voxel size 1.3 × 1.3 × 3.0 mm3), T2W-BLADE (transversal, TR 3000 ms, TE 89 ms, flip angle 90°, 33 slices, Slice thickness 6 mm, FOV 400 × 400, voxel size 1.3 × 1.3 × 6.0 mm3), DWI (2D, transversal, TR 6270 ms, TE 50 ms, 33 slices, 6 mm slice thickness, FOV 400 × 400, voxel size 1.6 × 1.6 × 6.0 mm3, b-values 50, 800 s/mm2). The PET data were reconstructed using high-definition PET (HD-PET) (3 iterations, 21 subsets; matrix 172 × 172, voxel size 2.3 × 2.3 × 5.0 mm3). The DIXON sequence was used to derive MRI-based attenuation correction.
18F-FDG PET/CT imaging
Prior to 18F-FDG PET/CT scan, study participants were asked to fast for at least 6 h, ensuring the blood glucose (BG) less than 11.1 mmol/L, and then they were intravenously administered 18F-FDG (3.70–5.55 MBq/kg). All acquisitions were performed on a Biograph 64 PET/CT scanner (Siemens Healthcare, Erlangen, Germany) 45–60 min after 18F-FDG injection. The whole-body CT scanning parameters were set as follows: current (170 mA), voltage (120 kV), and scan layer thickness (3 mm). The PET scan was performed after CT scan acquisition. It was conducted in 5–6 bed positions. Per bed position, PET data were acquired with 2–3 min of acquisition time. Reconstruction of the acquired data was done by the postprocessing workstation with iterative TrueD reconstruction System (Siemens Medical Solutions), and correction attenuation was done by CT images.
All reconstructed PET/MR as well as PET/CT images were evaluated using Syngo.Via (Siemens Healthcare, Erlangen, Germany) by 2 experienced nuclear medicine physicians. Any difference between the two was solved by consensus.
Pancreatic masses were the target lesions. For lesions with an unclear boundary, contrast-enhanced CT or MR images were referenced during the segmentation. To calculate the standard uptake values (SUVs), circular regions of interest were drawn around the lesions and automatically adapted to a tridimensional volume of interest. For every lesion, the maximum SUV (SUVmax), mean SUV (SUVmean) as well as peak SUV (SUVpeak) were determined. SUVpeak was the SUVmean of a sphere sized 1-cm3 around the SUVmax in the target lesion. As a normal tissue reference, two circular regions of interest (ROIs) with the diameter of 2-cm were drawn in the right and left liver lobe. The averaged SUVmean of each ROI was used as the liver SUVmean. Calculation of tumor-to-liver ratio (TLR) was as: SUVmax of the tumor/SUVmean of liver.
If 68Ga-FAPI or 18F-FDG uptake surpassed the surrounding tissue, it was considered a positive lymph node. Distant metastases were assessed by tracer uptake as well as abnormalities in MR signal intensities. Locations of metastases were documented.
Data analyses were conducted using SPSS (version 26.0; IBM, Armonk, NY, USA). The quantitative data are presented as mean ± SD. The Wilcoxon signed-rank test was used to compare the number of primary as well as metastatic lesions, respectively identified by two examinations. We used a paired t-test to compare different paired 18F-FDG and 68Ga-FAPI PET SUV parameters. Correlation between 68Ga-FAPI with 18F-FDG SUVs was assessed by Pearson correlation test. p < 0.05 was the cutoff for significance, and all tests were two-sided.