Head-to-head intra-individual comparison of biodistribution and tumor uptake of 68Ga-FAPI and 18F-FDG PET/CT in cancer patients

Abstract

Purpose FAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this study is the head-to-head intra-individual comparison of 68Ga-FAPI versus standard-of-care 18F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers. Material and Methods This international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both 68Ga-FAPI and 18F-FDG PET/CT within a median time interval of 10 days (range 1–89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ). Results A total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions. 68Ga-FAPI uptake in primary tumors and metastases was comparable to 18F-FDG in most cases. The SUVmax was significantly lower for 68Ga-FAPI than 18F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus, 68Ga-FAPI TBRs were significantly higher than 18F-FDG TBRs in some sites, including liver and bone metastases. Conclusion Quantitative tumor uptake is comparable between 68Ga-FAPI and 18F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for 68Ga-FAPI. Thus, 68Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological 18F-FDG uptake.

FAP and FAPI-PET/CT in Malignant and Non-Malignant Diseases: A Perfect Symbiosis?

“…FAPI-PET/CT could therefore emerge as a supplement or replacement for FDG-PET/CT in a few instances. In large studies of multiple tumor types, FAPI-PET/CT demonstrated a superior diagnostic efficacy [123,124], a more accurate detection [125] and lower background activity [126]. Hence, FAPI may one day "overthrow" FDG from its oncological throne [127] (Figure 6).…”

FAP imaging in rare cancer entities—first clinical experience in a broad spectrum of malignancies

“…Rare tumors are of particular interest as most of them originate from epithelial tissue, particularly in head and neck and biliary tract cancers [8,9]. Additionally, FAPI might be useful for detecting peritoneal carcinomatosis, facilitating the diagnosis and guiding treatment which is rather challenging for tracers like 18 F-FDG due to high bowel activity and therefore extensive background accumulation [10,11]. Thus, it is of essence to evaluate the potential of 68 Ga-FAPIpositron emission tomography/computed tomography (PET/ CT) in rare diseases in order to utilize it most efficiently.…”

Radioligands Targeting Fibroblast Activation Protein (FAP)

“…Although the Standardized Uptake Values (SUVs) are similar between FAP-targeted tracers and [ 18 F]-FDG, the tumor-to-background ratios are considerably higher due to a lower accumulation in non-target tissues [ 34 ]. Imaging offers the best results in a time window of approximately 30–180 min after tracer injection, which is a significant advantage in terms of scheduling in clinical practice.…”

“…As reported by Giesel et al, Koerber et al and Syed et al, the gross tumor volumes for radiotherapy planning were frequently significantly larger in FAPI imaging compared to the standard imaging modalities of contrast-enhanced CT and/or MRI. Since the cancer associated fibroblasts are directly involved in the invasion of surrounding tissues and resistance to various therapies, a boosted radiation in areas with high FAP-activity might reduce the risk of recurrence from residual disease [ 34 , 48 , 49 ].…”