FAPI PET versus FDG PET, CT or MRI for Staging Pancreatic-, Gastric- and Cholangiocarcinoma: Systematic Review and Head-to-Head Comparisons of Diagnostic Performances

Abstract

Introduction: There is a pressing demand for the development of cancer-specific diagnostic imaging tools, particularly for staging of pancreatic-, gastric- or cholangiocarcinoma, as current diagnostic imaging techniques, including CT, MRI and PET using FDG, are not fully adequate. The novel PET-tracer “FAPI” has the potential to visualize even small tumour deposits employing the tumour-specific expression of fibroblast-activating protein (FAP) in malignant cells. Methods: We performed a systematic review to select studies investigating the use of FAPI PET for staging pancreatic-, gastric- and cholangiocarcinoma (PROSPERO CRD42022329512). Patient-wise and lesion-wise comparisons were performed for primary tumour (T), lymph nodes (N), organ metastases (M) and peritoneal carcinomatosis (PC). Maximum standardized uptake values (SUVmax) and tumour-to-background ratios (TBR) were compared between PET using FAPI versus FDG (if reported). Results: Ten articles met the inclusion criteria. In all studies, FAPI PET showed superiority over FDG-PET/CT/MRI for the detection of T, N, M and PC, both in the patient-wise and in lesion-wise comparisons (when performed). Additionally, higher SUVmax and TBRmax values were reported for use of FAPI compared to FDG. Conclusions: The positive results of this review warrant prospective clinical studies to investigate the accuracy and clinical value of FAPI PET for diagnosing and staging patients with pancreatic-, gastric- and cholangiocarcinoma.

68Ga-FAPI PET/CT Provides a Clear Picture of a Klatskin Tumor That 18F-FDG PET/CT Missed

“…In this case, the relatively novel radiotracer, 68 Ga-labeled FAPI, was successful in assessing primary Klatskin tumor and avoided the well-known false-negative pitfall of the more traditional 18 F-FDG, particularly for the histological mucinous subtype 1,2 . Indeed, this was in line with the expectations of colleagues in the field who have explored the comparable utility of 68 Ga-FAPI PET/CT in the oncologic field generally, as well as for tumors of biliary origin specifically 3–9 . According to Dendl et al, among others, the explanation could be found in the relatively unique tumor microenvironment of the major cholangiocarcinoma subtypes and the associated abundance of desmoplastic reactions and cancer-associated fibroblasts 10,11 .…”

Multimodality imaging of hepatocellular carcinoma and intrahepatic cholangiocarcinoma

“…As management of these subtypes differs, assessing tumor infiltration into the bile duct and surrounding tissues is essential but is often challenging. [7][8][9][10] e-CCA comprises perihilar cholangiocarcinoma (pCCA or Klatskin tumor), the most common form, and distal cholangiocarcinoma (dCCA), which occurs in 50% and 30%-40% of cases, respectively. 11 Globally, the prevalence of ICC has increased substantially by 109% over the last 10 years, from 0.67 per 100 000 in 2007 to 1.40 per 100 000 in 2016.…”

“…Cholangiocarcinoma (CCA) tumor includes the intrahepatic subtype above the second‐order bile ducts, which typically accounts for 10%–20% of cases, and extrahepatic subtypes (e‐CCA). As management of these subtypes differs, assessing tumor infiltration into the bile duct and surrounding tissues is essential but is often challenging 7–10 . e‐CCA comprises perihilar cholangiocarcinoma (pCCA or Klatskin tumor), the most common form, and distal cholangiocarcinoma (dCCA), which occurs in 50% and 30%–40% of cases, respectively 11 .…”

Imaging in translational cancer research

“…Apart from FDG and PSMA, several other tracers are currently being used and investigated in PET imaging, most prominently FAPI, which uses the tumor expression of fibroblast-activating protein (FAP) to diagnose and stage patients with cancers of the stomach or pancreas, and cholangiocarcinoma 210 . Other tracers are 18 F-fluoroethyl-L-tyrosine (FET) and 11 C-methionine (MET), which correlates with microvessel density in proliferating cells, both of which are used in glioma imaging; 68 Ga-DOTATOC (DOTA 0 -Phe 1 -Tyr 3 -octreotide), a somatostatin analog used to detect neuroendocrine tumors 211 ; and 11 C-metomidate PET, which is used to detect adrenal masses 212 .…”