Comparison of the Detection Performance Between FAP and FDG PET/CT in Various Cancers: A Systemic review and Meta-analysis

Wen-Yi Chang, PhD, Neng-Chuan Tseng, MD, Li-Yu Chen, MN, Chi-Wei Chang, PhD, Ya-Yao Huang, PhD, Ya-Ting Huang, PhD, Yen-Chuan Ou, MD, Nan-Jing Peng, MD, PhD

Published by Clinical Nuclear Medicine 48(2):p 132-142, February 2023.

Abstract

Purpose 
18F-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 SUVmax 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.