Comparison of ⁶⁸Ga-FAPI versus ¹⁸F-FDG PET/CT for Initial Cancer Staging

Take-Away Points

• ■ Major Focus: To compare ⁶⁸Ga-FAPI, a fibroblast-activated protein inhibitor (FAPI) coupled with radioactive gallium 68, with fluorine 18 fluorodeoxyglucose (¹⁸F-FDG) PET/CT.

• ■ Key Result: In a direct comparison, ⁶⁸Ga-FAPI PET/CT outperformed ¹⁸F-FDG PET/CT in sensitivity and specificity for primary, nodal, and metastatic lesion characterization across different tumor types.

• ■ Impact: ⁶⁸Ga-FAPI PET/CT is safe, and initial studies show it is more accurate than ¹⁸F-FDG PET/CT for oncologic staging. Additionally, coupled with its theranostic potential, ⁶⁸Ga-FAPI could become a widely used PET radiotracer in oncologic imaging in the future.

Currently, ¹⁸F-FDG PET/CT is the workhorse of oncologic nuclear medicine. ¹⁸F-FDG PET takes advantage of the propensity that most tumor cells consume high levels of glucose. However, accumulation of FDG by nonmalignant cells limits detection of cancer in tissue with high native glucose uptake, and not all cancer cells preferentially metabolize glucose. ¹⁸F-FDG PET/CT lacks specificity, as activated immune cells in tumors or inflammatory lesions also accumulate the radiotracer. Fibroblast-activated protein is expressed at very low levels throughout the body; however, it is highly expressed on cancer-associated fibroblasts. Therefore, ⁶⁸Ga-FAPI PET/CT may be more specific for imaging tumors.

Chen et al compared the standard uptake value of cancer lesions in 75 patients with 12 different tumor types who underwent both scans within 1 week. A per-lesion analysis showed greater sensitivity of ⁶⁸Ga-FAPI PET/CT for primary lesions (98.2% vs 82.1%, P = .021), metastatic nodes (86.4% vs 45.5%, P = .004), and bone and visceral metastases (83.8% vs 59.5%, P = .004) than ¹⁸F-FDG PET/CT, likely because of the higher tumor-to-background signal ratio for ⁶⁸Ga-FAPI. Biopsies of some discordant lesions did not find ⁶⁸Ga-FAPI PET/CT to be less specific than ¹⁸F-FDG PET/CT. In this initial study, authors also present some intriguing findings that might be a harbinger of limitations in larger and more diverse populations. One primary pancreatic cancer was not found on ⁶⁸Ga-FAPI PET/CT, likely because of high uptake of the whole gland due to concurrent pancreatitis. ⁶⁸Ga-FAPI PET showed false-positive findings not seen with FDG, namely a bone lesion due to myelofibrosis, a mass-forming liver cirrhotic lesion, and pleural thickening caused by mycobacterial infection. These false-positive findings all share benign fibrosis.

With FAPIs being tested in clinical trials for cancer treatment, ⁶⁸Ga-FAPI PET/CT may be applied both for detecting cancer and selecting patients for treatment.

Highlighted Article

• Chen H, Pang Y, Wu J, et al. Comparison of [⁶⁸Ga]Ga-DOTA-FAPI-04 and [¹⁸F] FDG PET/CT for the diagnosis of primary and metastatic lesions in patients with various types of cancer. Eur J Nucl Med Mol Imaging 2020;47;1820–1832. doi: https://doi.org/10.1007/s00259-020-04769-z