Comparison of physiological uptake of normal tissues in patients with cancer using 18F-FAPI-04 and 18F-FAPI-42 PET/CT

Mu, Xingyu; Huang, Xiaoxue; Li, Meng; Sun, Wenjie; Fu, Wei

doi:10.3389/fnume.2022.927843

Cited by 4 publications

(3 citation statements)

References 23 publications

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“…SEMA3A has been proposed as well as a major mediator of nerve regulation of bone turnover as well as a crosstalk factor between osteoblasts and osteoclasts (34,35) . Last, MMP-2 and FAP-α are proteases involved in fibrotic tissue remodeling whose mRNA levels were found significantly upregulated in previous studies and may be useful as circulating biomarkers or even targetable factors for FD therapy (9,15,18,(36)(37)(38)(39)(40) .…”

Section: Discussionmentioning

confidence: 92%

Transcriptomic signature and pro-osteoclastic secreted factors of abnormal bone marrow stromal cells in fibrous dysplasia

Michel,

Raborn,

Spencer

et al. 2024

Preprint

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Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants in GNAS, encoding for Gαs, which leads to excessive cAMP signaling in bone marrow stromal cells (BMSCs). Despite advancements in our understanding of FD pathophysiology, the effect of Gαs activation in the BMSC transcriptome remains unclear, as well as how this translates into their local influence in the lesional microenvironment. In this study, we analyzed changes induced by Gαs activation in BMSC transcriptome and performed a comprehensive analysis of their production of cytokines and other secreted factors. We performed RNAseq of cultured BMSCs from patients with FD and healthy volunteers, and from an inducible mouse model of FD, and combined their transcriptomic profiles to build a robust FD BMSC genetic signature. Pathways related to Gαs activation, cytokine signaling, and extracellular matrix deposition were identified. In addition, a comprehensive profile of their secreted cytokines and other factors was performed to identify modulation of several key factors we hypothesized to be involved in FD pathogenesis. We also screened circulating cytokines in a collection of plasma samples from patients with FD, finding positive correlations of several cytokines with their disease burden, as well as with other cytokines and bone turnover markers. Overall, these data support a pro-inflammatory, pro-osteoclastic behavior of BMSCs bearing hyperactive Gαs variants, and point to several cytokines and other secreted factors as possible therapeutic targets and/or circulating biomarkers for FD.

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Section: Discussionmentioning

confidence: 92%

Transcriptomic signature and pro-osteoclastic secreted factors of abnormal bone marrow stromal cells in fibrous dysplasia

Michel,

Raborn,

Spencer

et al. 2024

Preprint

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“…Three nuclear medicine physicians with 15, 10, and 8 years of experience in interpreting PET/CT and MR imaging determined the physiological and benign tracer uptake regions based on the patients’ clinical data, imaging data (CT, MRI, 18 F-FDG PET, or ultrasound), histopathology, and their own experiences in image interpretation. Physiological uptake refers to the slightly elevated uptake of 68 Ga-FAPI-04 in generally normal tissues, which usually show no abnormal changes on other imaging modalities ( 20 , 21 ). Benign uptake refers to inflammation, fibrosis, benign tumors, and other non-malignant tumor regions that may be abnormal on other imaging modalities ( 16 , 22 ).…”

Section: Methodsmentioning

confidence: 99%

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

Wang

et al. 2022

Front. Oncol.

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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.

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“…Along with the crucial advantage that amino acid tracers can easily permeate across the BBB (whether the BBB is compromised or not), this pathway is thus more specific in highlighting "live" proliferating cells rather than structural changes. On the other hand, FAPI ligands do not cross the BBB and hence may offer an additional complementary representation of tumor characteristics (10,11). Other amino acid radioligands such as α-[ 11 C]-methyl-l-tryptophan (AMT) and 18 F-Fluciclovine (FACBC), as well as glutamine-based amino acids are under evaluation for their potential in tumor characterization, prognostication, viable volume delineation and detection of recurrence in brain tumors and metastases (12).…”

Section: Introductionmentioning

confidence: 99%

Tumor microenvironment and fibroblast activation protein inhibitor (FAPI) PET: developments toward brain imaging

et al. 2023

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Fibroblast activation protein (FAP) is a type-II membrane bound glycoprotein specifically expressed by activated fibroblasts almost exclusively in pathological conditions including arthritis, fibrosis and cancer. FAP is overexpressed in cancer-associated fibroblasts (CAFs) located in tumor stroma, and is known to be involved in a variety of tumor-promoting activities such as angiogenesis, proliferation, resistance to chemotherapy, extracellular matrix remodeling and immunosuppression. In most cancer types, higher FAP expression is associated with worse clinical outcomes, leading to the hypothesis that FAP activity is involved in cancer development, cancer cell migration, and cancer spread. Recently, various high selectivity FAP inhibitors (FAPIs) have been developed and subsequently used for positron emission tomography (PET) imaging of different pathologies. Considering the paucity of widely available and especially mainstream reliable radioligands in brain cancer PET imaging, and the poor survival rates of patients with certain types of brain cancer such as glioblastoma, FAPI-PET represents a major development in enabling the detection of small primary or metastatic lesions in the brain due to its biological characteristics and low background accumulation. In this work, we aim to summarize the potential avenues for use of FAPI-PET, from the basic biological processes to oncologic imaging and with a main focus on brain imaging.

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Comparison of physiological uptake of normal tissues in patients with cancer using 18F-FAPI-04 and 18F-FAPI-42 PET/CT

Cited by 4 publications

References 23 publications

Transcriptomic signature and pro-osteoclastic secreted factors of abnormal bone marrow stromal cells in fibrous dysplasia

Transcriptomic signature and pro-osteoclastic secreted factors of abnormal bone marrow stromal cells in fibrous dysplasia

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

Tumor microenvironment and fibroblast activation protein inhibitor (FAPI) PET: developments toward brain imaging

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