68Ga-FAPI PET/MR is Helpful in Differential Diagnosis of Pancreatitis From Pancreatic Malignancy Compared to 18F-FDG PET/CT

Background: 68 Ga-broblast activation protein specic enzyme inhibitor (FAPI) is a novel PET agent for tumor imaging. Case description: We herein present a case where 68 Ga-FAPI PET/MR helped to diagnose IgG4-RD that involved pancreas and bile duct. Our 62-year-old patient suffered from middle upper abdomen and brown urine. Blood test revealed abnormal liver function and elevated IgG4 (4.830g/L ↑ ). 18 F-FDG PET showed enlarged uncinate process and dilated bile duct tree. Mild increase of FDG uptake in uncinate process and head of pancreas indicated possible pancreatic malignancy, but the evidence was not sucient enough. 68 Ga-FAPI PET revealed prominent broblast mediated inammation in the entire pancreas and bile duct, suggesting IgG4-RD. Conclusion: The case illustrates that 68 Ga-FAPI PET is more sensitive to IgG4-RD than 18 F-FDG, and thus could be helpful in improving the differential diagnosis of pancreatitis and pancreatic cancer.

Background 18 F-FDG PET/CT imaging is gaining increasing use in clinical applications, but it has still some limitations in the differential diagnosis of in ammatory or malignant pancreatic diseases [1]. This is mainly due to the fact that 18 F-FDG is a non-speci c imaging agent. In most cases, both tumorous and in ammatory disease show high radioactivity at the lesion site, while in other cases, tumor lesions and in ammatory lesions show mild or normal uptake of radioactivity in the involved organs. This makes differential diagnosis di cult for neoplastic diseases and in ammatory disease. For instance, when autoimmune pancreatitis appears to be hypermetabolic in a focal area, it can be mistaken for pancreatic malignancy [1,2].
Radiolabelled FAPI is a newly developed tumor imaging tracer which targets broblast activation protein (FAP) [3,4]. The speci city of FAPI imaging in tumor is better than FDG,and in some speci c in ammations (such as IgG4-RD, rheumatoid disease, etc.), FAPI also has a better effect than FDG due to the active brogenic reaction [5]. Therefore, when FDG imaging is limited in differentiating in ammation from tumor lesions, FAPI imaging can provide important clue and yield more accurate diagnosis.

Case Description
A 62-year-old man who had diffuse discomfort in middle upper abdomen, accompanied by brown urine.
Blood test showed abnormal liver function, with IgG4 4.830g/L↑. Ultrasound gastroscopy showed uneven internal high-low echo and poor internal blood signal in pancreatic neck lesion, (size about 2.0×2.5 cm 2 ) with clear boundary. The lesion was located adjacent to the portal vein and superior mesenteric vein. No obvious expansion of the main pancreatic duct in the body and tail pancreas was found. Possible malignancy was considered.
MRCP (Magnetic Resonance Cholangiopancreatography) showed that the intrahepatic bile duct was slightly dilated, common bile duct was dilated, in ammation of lower segment of common bile duct was possible, and the malignancy could not be excluded.
Thin-slice enhanced CT scan of pancreas showed the uncinate process of pancreatic head lesion, suggesting possible malignancy with intrahepatic and extrahepatic bile duct dilatation.
In order to identify the nature of pancreatic lesions, further PET/CT scanning was performed. 18 F-FDG PET/CT showed the uncinate process of pancreas was mildly enlarged with bile duct tree dilated, the FDG metabolism was slightly increased in uncinate process and head of pancreas (SUV max =4.07, SUV mean =2.25, 2.4cm*1.8cm), the possibility of malignant tumor was considered. (Fig. A-D).
After two weeks of symptomatic treatment, the liver function improved signi cantly. However, as the above modalities could not exclude the possibility of pancreatic malignancy, 68 Ga -FAPI PET/MR scanning was recommended.
According to the PET/MR scan (Fig. E-H), 68 Ga-FAPI uptake was evenly elevated in the entire pancreas (SUV max =11.04, SUV mean =6.15). Increased 68 Ga-FAPI uptake was also found around dilated intrahepatic and extrahepatic bile duct (SUV max =3.61, SUV mean =1.92). PET/MR diagnosed unequivocally IgG4-RD that involved pancreas and intrahepatic and extrahepatic bile duct. Discussion 18 F-FDG PET has many advantages over other imaging modalities (such as CT, MR, B-ultrasound), but there are still challenges in differentiating autoimmune pancreatitis from pancreatic cancer [5], especially in focal autoimmune pancreatitis when there is no indication of in ammation involved in other related organs (such as salivary glands,orbit, thyroid, lung, retroperitoneal, kidney, lymph node, etc) [6]. 68 Ga-FAPI is a radiolabelled agent targeting the inhibitor of broblast activation protein (FAP), which is often present in tumor stroma [3,4], in addition to in ammatory tissue with prominent broblast proliferation as plasma cell mediated sclerosing in ammation [5,7]. The sensitivity of 68 Ga-FAPI to IgG4-RD is signi cantly higher than that of 18 F-FDG. In this case, 68 Ga-FAPI PET showed the in ammation involving the whole pancreas and bile duct tree, which could not be detected by 18 F-FDG. This demonstrated that 68 Ga-FAPI was not more tumor-speci c than 18 F-FDG, but it may be more sensitive than FDG in detecting prominent broblast mediated in ammation as IgG4-RD.

Conclusion
This case demonstrated that 68 Ga-FAPI PET is more sensitive to IgG4-RD compared with 18 F-FDG, and thus could be helpful in improving the differential diagnosis of pancreatitis and pancreatic cancer.

Declarations
Author contributions YS, JZ have made substantial contributions to conception and design of the case. YS, JZ and QX are involved in drafting the manuscript. JY and QX are responsible for the layout end the images. JZ had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the nal manuscript.

Con ict of interest
The authors declare that they have no con ict of interest.

Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Consent for publication
Informed consent was taken from the patient for the publication of this case report and related imaging.

Availability of data and material
The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.