⁶⁸Ga-FAPI PET/CT Outperforms FDG PET/CT in the Early Detection of the Carcinoma Gall Bladder

Gallbladder carcinoma contributes almost half of all biliary tract cancer.^[1] It often develops gradually, with early symptoms resembling biliary colic or cholecystitis, leading to late-stage diagnosis in most cases. Therefore, early diagnosis and treatment is crucial to improve the prognosis of patients with gallbladder cancer. ⁶⁸Ga labelled fibroblast activation protein inhibitor (FAPI), a promising PET tracer has shown a superior diagnostic efficacy than ¹⁸F-FDG for the diagnosis of primary and metastatic lesions in patients with various types of cancer.^[2–5]

¹⁸F-FDG, an analogue of glucose, reflects the expression of glucose transporter protein and glucose metabolism of the lesion^[6], but ⁶⁸Ga-FAPI-04 reflects the expression of the fibroblast activation protein (FAP) in the tumour stroma.^[7]Fibroblast activation protein (FAP) is a type II membrane bound glycoprotein that belongs to the dipeptidyl peptidase 4 family. It is highly expressed in cancer-associated fibroblasts (CAFs) of many epithelial carcinomas,^[8,9] particularly which are characterised by a strong desmoplastic reaction.^[10] In our case, moderately FAPI expressing gallbladder fundal lesion did not show increased uptake of FDG. The small size and low-grade tumour^[11–13] might be responsible for false negative result of gallbladder tumour on ¹⁸F-FDG PET/CT. The FAPI expression was higher in gallbladder tumour due to the possibility of a significant degree of fibrosis, desmoplastic reaction and therefore high expression of FAP.

In addition, ⁶⁸Ga-FAPI-04 PET/CT can be used for prognostic assessment, and usually high expression of FAP is associated with poor prognosis,^[7] as well as for postoperative efficacy monitoring, which may be more sensitive than ¹⁸F-FDG PET/CT.

A 58-year-old female presented with complaints of pain in the right hypochondrium for 2 weeks. Ultrasonography showed cholelithiasis with no definite evidence of cholecystitis. Computed tomography (CT) of the abdomen revealed an equivocal hyperdense thickened anterior wall of the gallbladder. Magnetic resonance cholangiogram with contrast was suggestive of the focal thickened anterior wall of the fundus of the gallbladder with signal characteristics and arterial enhancement pattern strongly suspicious for neoplasm. Fluorodeoxyglucose positron emission tomography/CT (FDG PET/CT) revealed non-FDG-avid focal enhancing thickening of the gallbladder fundus (maximum thickness 6 mm), extending for a length of 2.5 cm approximately [Fig 1]. In view of no significant FDG avidity, the possibility of the carcinoma was less likely. Therefore, for better characterisation, fibroblast activation protein inhibitor (FAPI) PET/CT was suggested, which revealed moderately increased FAPI expression in the same lesion (SUVmax 5.7), highly indicative of malignant aetiology with no evidence of metastatic disease [Fig 2]. Further, the patient was taken up for the laparoscopic radical cholecystectomy along with pericystic and periportal lymph node dissection. Surgical histopathology revealed moderately differentiated adenocarcinoma with sclerosis of the gallbladder infiltrating the wall deeply with negative nodes and free hepatic margins (pT2aN0M0). The patient was referred for chemotherapy.

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Fig 1: (a and b) Computed tomography (CT) images; (c and d) Corresponding fluorodeoxyglucose (FDG) positron emission tomography/CT images, and (e) Maximum intensity projection image revealed non-FDG-avid focal enhancing thickening of the gallbladder fundus (maximum thickness 6 mm), extending for a length of 2.5 cm approximately (thin white arrows in a-d)

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Fig 2: (a and b) Computed tomography (CT) images; (c and d) corresponding fibroblast activation protein inhibitor (FAPI) positron emission tomography/CT images, and (e) Maximum intensity projection image revealed FAPI expressing focal hyperdense eccentric thickening along anterior wall of the gallbladder fundus (SUVmax 5.7) (thin white arrows in a-d; thin black arrow in e) with no distant or locoregional metastatic lesion. SUV: Standardised uptake value

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