Comparison of the Detection Performance Between FAP and FDG PET/CT in Various Cancers

Abstract

Purpose: 18 F-FDG is the dominant radiotracer in oncology; however, it has limitations. Novel labeled fibroblast activation protein (FAP) radiotracers have been developed and published in several studies. Thus, this meta-analysis aimed to compare the detection rates (DRs) of FDG and FAP, based on previous studies from a systematic review. Methods: PubMed/MEDLINE and Cochrane library databases were used to perform a comprehensive and systematic search and are updated to April 30, 2022. The DR, relative risk, and the SUV max were calculated between the FAP and FDG tracers. Finally, the sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curve of FAP and FDG were analyzed using gold and reference standards. Results: Thirty studies (1170 patients) were included in the meta-analysis. The relative risks of FAP DR for the primary tumor, recurrent tumor, lymph node metastasis, and distant metastasis were FDG 1.06-to 3.00-fold per patient and per lesion. For the primary tumor, FAP uptake was most intense in pancreatic cancer, followed by head and neck, cervical, colorectal, lung, gastric, and hepatocellular carcinoma, and was higher than FDG except for urological system cancer. The sensitivity (0.84-0.98), diagnostic odds ratio (19.36-358.47), and summary receiver operating characteristic curve (0.94-0.99) of FAP based on patient and lesion were better for primary tumors, LN metastasis, and distant metastasis than FDG. Conclusions: Fibroblast activation protein is an extremely potential radiotracer to replace most of the use of FDG in oncology. It is noteworthy that the FAP tracers for primary tumors had low specificity despite excellent sensitivity and had lower uptake than FDG in urological system cancer. In addition, the difference in detection between FAP and FDG for LN metastasis could not be certain in sarcoma.

Use of Fluoro-[18F]-Deoxy-2-D-Glucose Positron Emission Tomography/Computed Tomography to Predict Immunotherapy Treatment Response in Patients With Squamous Cell Oral Cavity Cancers

“…We did not observe correlations between change in primary OCSCC FDG uptake from baseline to early ( ~ 3 weeks) after starting preoperative immunotherapy and pathologic response at surgery in either the nivolumab or nivolumab plus ipilimumab treatment arms. We did not observe an early increase in tumor FDG uptake after starting preoperative immunotherapy (or “flare phenomenon”) due to infiltration of immune effectors cells in responding tumors as previously reported in 2 studies of melanoma . The lack of correlation may be related to the complexity of the whole tumor composition at the early time point, including viable and nonviable tumor cells, fibrosis, necrosis, and immune effector cells.…”

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 .…”

“…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][4][5][6][7][8][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 This, combined with FAPI's significantly lower background (liver) uptake, results in excellent target-to-background ratios and, as a result, improved sensitivity for not only the primary tumor, but also metastatic nodal and distant carcinomatosis.…”

Unusual Metastasis of Signet-Ring Cell Gastric Cancer That Could Not Be Detected With 18F-FDG PET But With 68Ga-FAPI PET/CT

“…1 68 Ga-labeled FAP inhibitors are novel and prominent PET radiopharmaceuticals with applicability across various tumor types. [2][3][4][5] In gastric cancers, signet ring cell and mucinous carcinomas often exhibit low FDG affinity, 6,7 a characteristic that can occasionally complicate physicians' interpretation of 18 F-FDG PET/CT imaging. Recent studies have demonstrated that 68 Ga-FAPI PET/CT outperforms 18 F-FDG PET/CT in these specific subtypes, particularly in peritoneal carcinomatosis.…”