Non-tumoral uptake of 68Ga-FAPI-04 PET: A retrospective study

Abstract

ObjectiveFibroblast activation protein (FAP)-targeting radiopharmaceutical based on the FAP-specific inhibitor (FAPI) is considered as a potential alternative agent to FDG for tumor-specific imaging. However, FAP is also expressed in normal adult tissues. The aim of this study was to explore the image features of non-tumoral regions with high uptake of 68Ga-FAPI-04 in positron emission tomography (PET) imaging and to reveal the physiological mechanisms of these regions.MaterialA total of 137 patients who underwent whole-body 68Ga-FAPI-04 PET/MR (n=46) or PET/CT (n=91) were included in this retrospective study. Three experienced nuclear medicine physicians determined the non-tumoral regions according to other imaging modalities (CT, MRI, 18F-FDG PET, or ultrasound), clinical information, or pathological results. The regions of interest (ROIs) were drawn manually, and the maximum standardized uptake value (SUVmax) was measured.ResultsA total of 392 non-tumoral uptake regions were included in this study. The included physiological regions were uterus (n=38), submandibular gland (n=118), nipple (n=37), gingiva (n=65), and esophagus (n=31). The incidence of 68Ga-FAPI-04 uptake in physiological regions was independent of age, the tracer uptakes in the gingiva and esophagus were more common in male patients (p=0.006, 0.009), while that in the nipple was more common in female patients (p < 0.001). The included benign regions were inflammatory lymph node (n =10), pneumonia (n=13), atherosclerosis (n=10), pancreatitis (n=18), osteosclerosis (n=45), and surgical scar (n=7). No significant difference was observed in SUVmax between physiological and benign regions.ConclusionsA number of organs exhibit physiological uptakes of 68Ga-FAPI-04. Our study showed that regions with high 68Ga-FAPI-04 uptake did not necessarily represent malignancy. Being familiar with physiological and typical benign 68Ga-FAPI-04 uptake regions can be helpful for physicians to interpret images and to make an accurate diagnosis.

Multiparametric Characterization of the DSL-6A/C1 Pancreatic Cancer Model in Rats

“…So far, the FAP expression of DSL-6A/C1 has not been investigated, but it will be the topic of a future study. Furthermore, 68 Ga-FAPI uptake can not only be seen in CAF, but also in non-malignant conditions, such as inflammatory lymph nodes, artherosclerosis, or surgical scars [59]. Nevertheless, the high tracer uptake is described in 68 Ga-FAPI PET images obtained from human PDAC patients [22,60].…”

Nonmalignant 68Ga-FAPI-46 Uptake in 2 Cases of TENIS Syndrome

“…5 Factors such as age, presence of fibroids, and uterine volume can influence the visualization of the uterus in a 68 Ga-FAPI scan. 4,6,7 Another example is the gallbladder, where FAP expression is high in glandular cells. Therefore, physiologic uptake of FAPI can be observed in the gallbladder during scan.…”

“…The high physiological uptake in the uterus can overlap with malignancies, due to angiogenesis, tissue remodeling, and fibrogenesis 5 . Factors such as age, presence of fibroids, and uterine volume can influence the visualization of the uterus in a 68 Ga-FAPI scan 4,6,7 . Another example is the gallbladder, where FAP expression is high in glandular cells.…”

Highlighting Fibroblasts Activation in Fibrosis: The State-of-The-Art Fibroblast Activation Protein Inhibitor PET Imaging in Cardiovascular Diseases

“…In addition, [ 68 Ga]Ga-FAPI uptake in the right ventricle (RV) was observed in pressure overload cardiac diseases, such as idiopathic pulmonary arterial hypertension (IPAH) and hypertensive heart disease [54,56]. Likewise, investigation of FAPI PET in vascular diseases, such as thrombosis and atherosclerosis, was initiated because of accidental FAPI uptake in patients with various diseases [70,[72][73][74].…”