Comparison of 18F-FDG and 68Ga-FAPI-04 Uptake in Postoperative Re-evaluation of Gastric, Duodenal, and Colorectal Cancers : Clinical Nuclear Medicine

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Comparison of 18F-FDG and 68Ga-FAPI-04 Uptake in Postoperative Re-evaluation of Gastric, Duodenal, and Colorectal Cancers

Liu, Huipan MD, PhD∗,†,‡,§; Yang, Xiao MD; Liu, Lin MBBS∗,†,‡,§; Qu, Gengcuo MD∗,†,‡,§; Chen, Yue MD∗,†,‡,§

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Clinical Nuclear Medicine 48(4):p 304-308, April 2023. | DOI: 10.1097/RLU.0000000000004604
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Gastric cancer and colorectal cancer, common types of gastrointestinal cancer, comprised 10.6% (ranked third) and 6.1% (ranked fifth) of all cancers diagnosed in 2018.1,2 Complete surgical resection of gastrointestinal cancer is considered a potential cure, but its long-term survival is often reported to be poor. The detection of tumor recurrence and metastasis is important for the management of patients. 18F-FDG PET/CT is a widely accepted tumor imaging method with important implications in various cancers.3,4 However, 18F-FDG uptake multiplicity has been noted in PET studies of gastrointestinal patients, especially lower uptake in some specific histological subtypes, such as adenocarcinoma and signet ring cell carcinoma.5,6 Furthermore, the diagnostic effect of 18F-FDG is limited, as the variable physiological uptake of 18F-FDG in the gastrointestinal tract may interfere with the detection of foci and require intensive monitoring from time to time.7 Therefore, the development of an effective PET tracer is expected to improve the characterization of gastrointestinal tumors and facilitate the precise diagnosis of patients.

68Ga-FAPI has been developed and used for targeting fibroblast-activation protein and visualization of tumor stroma, which showed a higher sensitivity than 18F-FDG in the detection of primary and metastatic lesions of various types of cancers.8,9 However, the role of 68Ga-FAPI PET/CT in patients with gastric, duodenal, and colorectal cancers after operation is not clear. In this study, we aimed to analyze the value of 68Ga-FAPI-04 PET/CT in the follow-up of postoperative patients with gastrointestinal cancer.



This retrospective study was conducted at the Affiliated Hospital of Southwest Medical University from January 2020 to June 2022. This study was approved by the ethics committee of our hospital (AHSWMU-2020-035), and informed consent was obtained from each patient. Inclusion criteria were biopsy-proven recurrent gastric, duodenal, and colorectal cancers or suspected disease recurrence, nodal and distant metastases based on other imaging tests, tumor markers, or clinical symptoms or follow-up. Patients were excluded when they had received chemotherapy or radiotherapy within 4 weeks before the PET/CT scan.

Preparation of 18F-FDG and 68Ga-FAPI-04

18F-FDG was manufactured in accordance with the standard method using the coincidence 18F-FDG synthesis module (FDG-N; PET Science & Technology, China). We purchased the precursor FAPI-04 from MCE (MedChemExpress, USA). The 68Ga-FAPI-04 labeling was carried out according to the method described previously.10,11 The radiochemical purity of 68Ga-FAPI-04 and 18F-FDG exceeded 95%. The final product is sterile and meets all of our institution's required standards before use.

PET/CT Imaging

For 18F-FDG PET/CT image acquisition, patients fasted for at least 6 hours, and the plasma glucose level is lower than 11 mmol/L.12 After intravenous injection of 18F-FDG (3.7 MBq/kg), the patient rested in a quiet place. The patients were instructed to drink 500 mL of water to stimulate 18F-FDG excretion in the renal calyx and to urinate before scanning. Data were acquired using a PET/CT scanner (uMI780; United Imaging, China) 45 to 60 minutes after intravenous administration. First, the CT image acquisition was performed from the head to the upper thigh segment (tube current of 120 mA, tube voltage of 120 kV, and slice thickness of 3.00 mm). PET was then performed at the same bed position as the CT scan, 5 to 6 bed positions, and 3D acquisition mode at 1.5 min/position. 68Ga-FAPI-04 PET/CT was performed within 7 days of 18F-FDG PET/CT for comparison, and the dose of 68Ga-FAPI-04 injected was calculated based on patient body weight (1.85 MBq/kg). Other parameters of CT or PET were the same as 18F-FDG PET/CT, except that 68Ga-FAPI-04 PET imaging was acquired at 3.0 min/position. After the reconstruction is complete, image analysis is performed using the joint imaging postprocessing fusion software.

PET/CT Imaging Review

Both 18F-FDG and 68Ga-FAPI-04 PET/CT images were interpreted in random order by 2 experienced nuclear medicine physicians. Any differences of opinion will be resolved by consensus. Based on knowledge of the normal biodistribution of 18F-FDG and 68Ga-FAPI-04, lesions were identified as positive if increased tracer uptake was noted in the normal contralateral structure and surrounding soft tissues. Lesions were characterized as either positively or possibly abnormal if the uptake of 18F-FDG and 68Ga-FAPI-04 was markedly to moderately increased. Diffuse mild or no increase in activity (in the absence of an abnormality on CT and no corresponding abnormality on PET) was considered normal or benign disease.

Tumors recurrence, individual lymph nodes, and lesions in the brain, lung, liver, peritoneum, mesentery, omentum, pleura, and bone were coded as positive if the activity exceeded that of adjacent background tissues. Individual lymph nodes were then classified into 8 sites, including the neck, supraclavicular, axilla, mediastinum (including epicardial, internal mammary, diaphragmatic lymph nodes), pulmonary hilum, abdomen (including para-aortic, porta hepatis, retroperitoneal, celiac), iliac, and inguinal regions.9 Brain, lung, liver, peritoneum, mesentery, omentum, pleura, and bone were each classified as individual sites. The SUVmax values were recorded for each site for both 18F-FDG and 68Ga-FAPI-04. If multiple positive lesions occurred at any one site, the average SUV was used, which was obtained by averaging the SUVs of all lesions (≤5) or the SUVs of the 5 lesions with the highest activity (>5).9

Reference Standard

68Ga-FAPI-04 and 18F-FDG PET/CT findings were validated by pathology as the criterion standard. In the case of the absence of pathological correlation, clinical and radiologic follow-up findings up to at least 3 months were taken into consideration to validate the 68Ga-FAPI-04 and 18F-FDG PET/CT findings.

Statistical Analysis

All statistical analyses were performed using SPSS software (version 22.0; IBM, Armonk, NY). Paired-samples t test was used to compare the SUVmax of tumor recurrence, lymph node, and distant metastases of 18F-FDG and 68Ga-FAPI-04 PET/CT. Results from the visually interpreted PET/CT images were compared with histopathology or follow-up results. We compared the statistical differences in detection rates of tumor recurrence, lymph nodes, and visceral metastases by 18F-FDG and 68Ga-FAPI-04 PET/CT using the McNemar test. P < 0.05 was considered to indicate a statistically significant difference.


Patient Characteristics

Between January 2020 and June 2022, 41 patients (25 men, 16 women; median age, 51 years; interquartile range, 19–75 years) were included in this study. Among these patients, 10 (24%) had gastric cancer, 28 (68%) had colorectal cancer, and 3 (7%) had duodenal carcinoma. Among these 41 patients, 39 (95%) had adenocarcinomas, and 2 (5%) had signet ring cell carcinomas. Patient characteristics are summarized in Table 1.

TABLE 1 - Summary of Patient Characteristics
Characteristic Value
No. patients 41
Age, y
 Median 51
 Interquartile range 19–75
 Male 25
 Female 16
 Gastric cancer 10
 Colon cancer 19
 Rectal cancer 9
 Duodenal cancer 3
Patient status
 Resection surgery 30
 Chemotherapy after surgery 11
Histologic findings
 Adenocarcinoma 39
 Signet ring cell carcinoma 2

Comparative Results for Recurrence Detection

Seventeen of 41 participants had 17 positive anastomotic stoma uptakes that were detected by means of either 68Ga-FAPI-04 or 18F-FDG PET. Tumor recurrence was correctly determined with use of 68Ga-FAPI-04 in 6 of 17 participants (false-positive uptake in 7 participants, true-negative uptake in 4 participants), whereas 4 of 17 participants were correctly diagnosed with use of 18F-FDG PET/CT (false-positive uptake in 10 participants, false-negative uptake in 2 participants, and true-negative uptake in 1 participant). Pathologic examination served as the reference standard for 12 of 17 participants, and morphologic imaging and/or follow-up imaging for the other 5 participants. Finally, 6 positive participants in 17 participants were diagnosed as tumor recurrence.

Regarding the 6 participants in whom recurrence was detected, the true-positive rates for 18F-FDG PET/CT and 68Ga-FAPI-04 PET/CT were 67% (4/6) and 100% (6/6), respectively (on a per-patient basis) (Fig. 1). Conversely, the true-negative rates of 68Ga-FAPI-04 and 18F-FDG PET/CT in the detection of recurrence were 80% (28/35) and 71% (25/35), respectively (on a per-patient basis). For the detection of recurrence, there was no evidence of a higher SUVmax for 68Ga-FAPI-04 PET than 18F-FDG PET (5.4 ± 3.4 vs 3.4 ± 0.4; P = 0.358) (Table 2). Six participants were misdiagnosed as tumor recurrence at both 68Ga-FAPI-04 and 18F-FDG PET/CT, which were finally confirmed as inflammation of anastomosis. In addition, 1 participant with anastomotic fibrosis was misdiagnosed as tumor recurrence on 68Ga-FAPI-04 but negative in 18F-FDG. 68Ga-FAPI-04 shows better detection performance in recurrent lesions than 18F-FDG PET/CT.

A 29-year-old man who presented with abdominal pain for more than 10 days. The patient underwent curative resection for transverse colon adenocarcinoma 1 year ago. Images from 18F-FDG PET/CT (AC) demonstrated no abnormal uptake throughout the whole body. 68Ga-FAPI-04 PET/CT (DF) showed increased tracer uptake in the anastomotic thickening (curved arrows, SUVmax of 10.4), which was confirmed tumor recurrence by gastroscopy, with multiple nodal (thin arrows, SUVmax of 9.7) and distant metastases (thick arrows, SUVmax of 10.9).
TABLE 2 - SUVmax Comparison Between 18F-FDG and 68Ga-FAPI-04 PET/CT in the Tumor Recurrence and Nodal and Distant Metastases
Index Tumor Recurrence Nodal Metastasis Distant Metastasis
18F-FDG SUVmax 3.4 ± 0.4 6.5 ± 3.6 8.9 ± 5.0
68Ga-FAPI-04 SUVmax 5.4 ± 3.4 8.3 ± 3.8 9.1 ± 5.1
P 0.358 0.002 0.886
Data are means ± SDs.

Diagnostic Performance of 18F-FDG and 68Ga-FAPI-04 PET/CT in Nodal Metastasis

Twenty-one of 41 participants had 103 positive lymph nodes that were detected by means of either 68Ga-FAPI-04 or 18F-FDG PET. Lymph node involvement was correctly determined with use of 68Ga-FAPI-04 in 92 of 103 lymph nodes (false-positive uptake in 2 lymph nodes, true-negative uptake in 9 lymph nodes), whereas 31 of 103 lymph nodes were correctly diagnosed with use of 18F-FDG PET/CT (false-positive uptake in 11 lymph nodes and false-negative uptake in 61 lymph nodes). Pathologic examination served as the reference standard for 8 of 103 lymph nodes, and morphologic imaging and/or follow-up imaging for the other 95 lymph nodes. Finally, 92 positive lymph nodes in 20 participants were diagnosed as nodal metastases.

The nodal metastases were localized in only the abdomen in 7 participants; only the iliac regions in 4 participants; supraclavicular, axilla, mediastinum, abdomen, and iliac regions in 2 participants; mediastinum and pulmonary in 2 participants; the abdomen and supraclavicular fossa in 2 participants; the pulmonary hilum in 1 participant; mediastinum, pulmonary hilum, and abdomen in 1 participant; and neck, supraclavicular, axilla, mediastinum, abdomen, and iliac regions in 1 participant.

Among the 92 nodal metastases, 61 nodal metastases (including 23 abdomen lymph nodes, 11 mediastinum lymph nodes, 12 supraclavicular fossa lymph nodes, 9 iliac regions lymph nodes, 5 neck lymph nodes, and 1 pulmonary hilum lymph node) were missed at 18F-FDG PET. The sensitivity of 68Ga-FAPI-04 PET/CT was higher than that of 18F-FDG PET/CT for detecting nodal metastases (92 of 92 [100%] vs 31 of 92 [34%]) (Fig. 2). For the metastatic lymph nodes, there was evidence of a higher SUVmax for 68Ga-FAPI-04 PET than 18F-FDG PET (8.3 ± 3.8 vs 6.5 ± 3.6; P = 0.002) (Table 2). Two abdominal lymph nodes were misdiagnosed as nodal metastases at both 68Ga-FAPI-04 and 18F-FDG PET/CT. The 2 lymph nodes were finally confirmed as reactive.

A 40-year-old man with rectal mucinous adenocarcinoma had a recent increase in tumor markers (carcinoembryonic antigen, CA-199, CA-724) after radiotherapy and chemotherapy for 9 months after surgery. Images from both 18F-FDG PET/CT (AC, solid arrows) and 68Ga-FAPI-04 PET/CT (DF, dotted arrows) showed no increased tracer uptake in the anastomotic stoma, with a slightly increased 18F-FDG uptake in para-aortic lymph node (solid curved arrows, SUVmax of 1.0). In addition, 68Ga-FAPI-04 PET/CT showed multiple para-aortic nodal metastases (dotted curved arrows, SUVmax of 8.4).

Diagnostic Performance of 18F-FDG and 68Ga-FAPI-04 PET/CT in Distant Metastasis

68Ga-FAPI-04 PET/CT visualized 30 distant metastases (including 9 hepatic metastases; 6 peritoneal, omentum, and/or mesenteric metastases; 6 pulmonary metastases; 4 bone metastases; 3 abdominal wall metastases; 2 chest wall and pleural metastases) in 18 participants. The distant metastases were localized in only the liver in 3 participants; in the peritoneum, omentum, and mesentery in 4 participants; in the bone in 2 participants; in the abdominal wall in 2 participants; in the lung in 1 participant; in the bone and lung in 1 participant; in the lung and chest wall in 1 participant; in the lung and liver in 1 participant; in the abdominal and chest wall in 1 participant; and in the abdominal wall and peritoneum in 1 participant. 68Ga-FAPI-04 PET/CT missed 2 distant metastatic lesions in 1 participant (false-negative uptake in 2 lungs) (Fig. 3).

A 51-year-old woman with adenocarcinoma of the descending colon received 5 cycles of chemotherapy 4 months after surgery. 18F-FDG PET/CT (AC) demonstrated increased tracer uptake in the iliac region lymph nodes (thin arrows, SUVmax of 8.9), liver masses (thick arrows, SUVmax of 9.5), and lung nodules (curved arrows, SUVmax of 1.8). 68Ga-FAPI-04 PET/CT (DF) showed increased tracer uptake in the iliac region lymph nodes (thin arrows, SUVmax of 8.2) and liver masses (thick arrows, SUVmax of 4.5), without pulmonary nodule uptake (curved arrows). The lesions were finally confirmed to be multiple metastases by follow-up.

18F-FDG PET/CT missed 10 distant metastatic lesions in 9 participants (false-negative uptake in 4 peritoneum, omentum, and mesentery metastases; 3 liver metastases; 2 bone metastases; and 1 pleural metastasis). Based on all distant metastases analysis, there was no evidence of a higher SUVmax for 68Ga-FAPI-04 PET than 18F-FDG PET (9.1 ± 5.1 vs 8.9 ± 5.0; P = 0.886) (Table 2).

Changes in Oncologic Management After 68Ga-FAPI-04 PET/CT

Three patients found more lymph node metastases in 68Ga-FAPI-04 than 18F-FDG; 2 patients found lymph node metastases in 68Ga-FAPI-04, but 18F-FDG was negative; 2 patients had tumor recurrence and lymph node metastases detected by 68Ga-FAPI-04, but 18F-FDG was negative; in 1 patient, tumor recurrence and metastases were detected by 68Ga-FAPI-04, and only tumor recurrence was detected by 18F-FDG, and no lymph node metastases were found.


Postoperative follow-up and recurrence detection for gastrointestinal tumors are helpful for patient management. 68Ga-FAPI is a very promising tumor imaging agent, which represents a promising alternative to 18F-FDG.13 In this study, 68Ga-FAPI-04 PET/CT demonstrated a higher detection efficacy for tumor recurrence (6 of 6 [100%] vs 4 of 6 [67%]), nodal metastases (92 of 92 [100%] vs 31 of 92 [34%]), and distant metastases (28 of 30 [93%] vs 20 of 30 [67%]) in participants with gastric, duodenal, and colorectal cancers compared with the detection efficacy of 18F-FDG PET/CT. 68Ga-FAPI-04 PET/CT resulted in new oncologic findings in 8 of 41 participants compared with 18F-FDG PET/CT. Thus, PET/CT imaging using 68Ga-FAPI may be beneficial for the clinical management for patients with gastric, duodenal, and colorectal cancers. In tumor recurrence detection, 1 signet ring cell carcinoma and 1 adenocarcinoma were negative on 18F-FDG but positive on 68Ga-FAPI-04, which also shows the difference in the imaging principles of the 2 radiopharmaceuticals. 18F-FDG assessment of signet ring carcinoma subtypes (SRCC) is unreliable; these tumors exhibit lower 18F-FDG uptake than other tissue tumors and may be missed entirely.14 Overall, the exact role of 18F-FDG PET/CT in the detection of recurrent gastrointestinal cancer remains unclear, and our study shows that 68Ga-FAPI outperforms 18F-FDG for recurrence detection.

Lymph node staging is critical for the treatment and prognosis of patients with gastric, duodenal, and colorectal cancers. In our study, compared with 18F-FDG PET/CT, 68Ga-FAPI-04 PET/CT was more efficient in the detection of metastatic lymph nodes because there were many lymph nodes without 18F-FDG uptake. The high lymph node detection efficiency of 68Ga-FAPI-04 PET/CT facilitates accurate lymph node staging and helps guide clinicians to determine reasonable postoperative treatment options. However, we noted that 68Ga-FAPI uptake was also shown in reactive lymph nodes in our study, which is consistent with previous studies.13,15,1668Ga-FAPI is not a more tumor-specific imaging tracer than 18F-FDG for metastatic lymph node detection. Therefore, it is necessary to consider false-positive uptake in lymph nodes when performing 68Ga-FAPI PET/CT imaging.

In detecting distant metastases, 68Ga-FAPI-04 PET/CT detected more lesions than 18F-FDG PET/CT. In our study, 68Ga-FAPI-04 PET/CT detected 6 peritoneal metastases, whereas 18F-FDG was negative in 4 lesions. Recent studies have also demonstrated that 68Ga-FAPI-04 is superior to 18F-FDG for the detection of peritoneal carcinomatosis in patients with gastric cancer.17,18 Gastrointestinal tumors are prone to liver metastases, especially in more than half of the patients with colorectal cancer.19 For liver metastases, surgery is the only available curative treatment, increasing the 5-year survival rates up to 40%.20 However, previous studies showed that, on a per-lesion basis, the 18F-FDG has a sensitivity of 62%, especially for small foci lesions, which may be due to physiological uptake in the liver.21 Our study shows that 68Ga-FAPI-04 can detect more liver metastasis lesions and facilitates postoperative liver metastasis monitoring. Moreover, in a published study, 68Ga-FAPI-04 PET was found to be more sensitive than 18F-FDG PET in detecting bone metastases, similar to our study.22 Interestingly, 2 lung metastases (diameter in 3 and 7 mm) were negative for 68Ga-FAPI-04 uptake, but positive for 18F-FDG, which is different from previous reports,9 and the specific reasons remain to be further analyzed.

Overall, in this study, 68Ga-FAPI-04 was found to show good results for the detection of tumor recurrence. For lymph node metastasis and distant metastasis, it is basically similar to the previous reports in the literature. In addition, studies also showed that the 68Ga-FAPI-04 has obvious advantages over the 18F-FDG, including a better tumor-to-background ratio, the independence of blood glucose levels, and the feasibility of rapid image acquisition.18

Our study has limitations. First, our study sample included a relatively small number of participants (n = 41). Second, because of technical and ethical concerns, histopathological confirmation of all positive lesions could not be performed, as all lymph nodes and distant metastases could not be biopsied; therefore, morphological and/or follow-up imaging results were also used as reference standards for our investigation. Third, because noninvasive imaging is itself a reference standard for tumor staging, the evaluation of possible false-negative lesions is incomplete.


68Ga-FAPI-04 PET/CT for tumor re-evaluation showed potential for more accurate performance of gastric, duodenal, and colorectal cancers, thereby improving treatment decision-making.


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18F-FDG; 68Ga-FAPI-04; bone and visceral metastases; lymph node metastasis; PET/CT

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