Abstract
PurposeFAPI 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 MethodsThis 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).ResultsA 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.ConclusionQuantitative 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.
Highlights
Altered metabolism is one of the hallmarks of cancer [1]
The first generation of radiolabeled fibroblast activation protein (FAP) inhibitors (FAPI) is peptidomimetic quinoline derivatives that bind with high affinity to FAP expressed on cancer-associated fibroblasts (CAFs)
The group of other cancers (n = 8) consists of a neuroendocrine bladder carcinoma, a prostate carcinoma, a B-cell lymphoma, a synovial sarcoma of the lung, an adrenal gland carcinoma, a malignant solitary fibrous cancer, and two cancers of unknown primary (CUP)
Summary
Altered metabolism is one of the hallmarks of cancer [1]. The metabolic switch to utilize glucose (often equated to the Warburg effect) has been successfully exploited by 18F-FDG PET imaging since the 1980s. 18F-FDG is the most frequently used tracer for oncological PET imaging. The metabolic switch to utilize glucose (often equated to the Warburg effect) has been successfully exploited by 18F-FDG PET imaging since the 1980s. PET imaging of the fibroblast activation protein (FAP) expression in cancer was recently introduced [4, 5]. The first generation of radiolabeled FAP inhibitors (FAPI) is peptidomimetic quinoline derivatives that bind with high affinity to FAP expressed on cancer-associated fibroblasts (CAFs). The tumor stroma consists of a variety of benign cells which interact with the tumor cells to promote growth, invasion, and metastasis. These cancer-associated cells, which are thought to promote tumor growth, often express unique receptors not found in the same cells outside of the tumor microenvironment.
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