A recent study published in the Journal of Nuclear Medicine has revealed that 68Ga-FAPI inhibitor, compared to 18F-FDG PET/CT or conventional CT, has superior tumor detection efficacy and tumor-to-background uptake for cholangiocarcinoma (CCA) and can aid in accurate staging for optimal treatment planning.

The study compared the accuracy of PET/CT imaging for managing cholangiocarcinoma using 68Ga-fibroblast activation protein (FAP) inhibitor (FAPI)-46 tracer, 18F-FDG PET/CT, and conventional CT. The study aimed to compare detection efficacy in 10 cholangiocarcinoma patients.

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Study results showed that 68Ga-FAPI-46 PET/CT demonstrated superior radiotracer uptake and lesion detection, especially in grade 3 tumors. Moreover, immunohistochemical analysis revealed high FAP expression on tumor stroma, making CCA a promising entity for 68Ga-FAPI-46 PET imaging.

In addition, 68Ga-FAPI-46 PET/CT demonstrated the highest detection efficacy for lymph nodes and distant metastases and higher SUVmax, measuring tumor uptake compared to 18F-FDG PET/CT and conventional CT. Moreover, 68Ga-FAPI-46 PET/CT did not affect intended therapies or trigger additional diagnostic tests, except in 1 case where it helped localize an unknown primary tumor. On the other hand, the accuracy of 18F-FDG was reportedly limited by intertumoral heterogeneous uptake.

The study highlighted that 68Ga-FAPI-46 PET/CT is superior to conventional CT scans and 18F-FDG PET/CT for staging CCA. Furthermore, based on a higher level of FAP, the FAP-targeted radioligand therapy (RLT) might become a valuable option for imaging and potentially treating CCA and other types of cancer, given its high expression in over 90% of human epithelial cancers.

“We confirm that 68GaFAPI-46 PET/CT is superior to 18F-FDG PET/CT, and also to conventional CT, for detection of primary tumor but especially for detection efficacy for lymph node and distant metastases,” the authors highlighted.

CCAs are a heterogenous group of liver malignancies developed within the biliary tract. They are becoming more familiar with rising incidence, often leading to fatal outcomes due to late diagnosis. Typically, MRI with MR cholangiopancreatography is used for primary tumor detection, with additional CT imaging for identifying distant metastases and vascular involvement.

While the current guidelines do not recommend PET/CT imaging for diagnosing and staging biliary tract malignancies, a novel radioactive tracer 18F-FDG is recommended for use, however, as its accuracy is limited by intertumoral heterogeneous uptake. Quinoline-based FAP–specific inhibitors coupled to 68Ga have recently been developed for PET imaging. The predominantly cancer-associated fibroblasts express the FAP inhibitors in the stroma of several tumor entities resulting in highly tumor-specific expression.

CCA having abundant tumor stroma composed of cancer-associated fibroblasts, is the promising tumor entity for 68Ga-FAPI 46 PET imaging. FAP is expressed in more than 90% of human epithelial cancers, making 68Ga-FAPI-46 a highly specific and effective tool for tumor detection.


Pabst KM, Trajkovic-Arsic M, Cheung PFY, et al. Superior tumor detection for 68Ga-FAPI-46 versus 18F-FDG PET/CT and conventional CT in patients with cholangiocarcinoma. Journal of Nuclear Medicine. Published online April 06, 2023. doi:10.2967/jnumed.122.265215