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

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4946
Author(s):  
Katharina Dendl ◽  
Stefan Koerber ◽  
Clemens Kratochwil ◽  
Jens Cardinale ◽  
Rebecca Finck ◽  
...  
Keyword(s):  
Heart Tissue ◽  
Peptidase Activity ◽  
Type Ii ◽  
Benign Diseases ◽  
Additional Information ◽  
Pet Ct ◽  
Transmembrane Serine Protease ◽  
Pathologic Processes ◽  
Pet Scans

A fibroblast activation protein (FAP) is an atypical type II transmembrane serine protease with both endopeptidase and post-proline dipeptidyl peptidase activity. FAP is overexpressed in cancer-associated fibroblasts (CAFs), which are found in most epithelial tumors. CAFs have been implicated in promoting tumor cell invasion, angiogenesis and growth and their presence correlates with a poor prognosis. However, FAP can generally be found during the remodeling of the extracellular matrix and therefore can be detected in wound healing and benign diseases. For instance, chronic inflammation, arthritis, fibrosis and ischemic heart tissue after a myocardial infarction are FAP-positive diseases. Therefore, quinoline-based FAP inhibitors (FAPIs) bind with a high affinity not only to tumors but also to a variety of benign pathologic processes. When these inhibitors are radiolabeled with positron emitting radioisotopes, they provide new diagnostic and prognostic tools as well as insights into the role of the microenvironment in a disease. In this respect, they deliver additional information beyond what is afforded by conventional FDG PET scans that typically report on glucose uptake. Thus, FAP ligands are considered to be highly promising novel tracers that offer a new diagnostic and theranostic potential in a variety of diseases.

scholarly journals Novel FAP ligands enable improved imaging contrast in sarcoma patients due to FAPI-PET/CT

2021 ◽  
Author(s):  
Stefan A. Koerber ◽  
R. Finck ◽  
K. Dendl ◽  
M. Uhl ◽  
T. Lindner ◽  
...  
Keyword(s):  
Hybrid Imaging ◽  
Background Activity ◽  
The Novel ◽  
Malignant Tissue ◽  
Primary Tumors ◽  
Aggressive Disease ◽  
Standardized Uptake Values ◽  
Pet Ct ◽  
Pet Scans

Abstract Purpose A high expression of fibroblast activation protein (FAP) was observed in multiple sarcomas, indicating an enormous potential for PET/CT using 68Ga-radiolabeled inhibitors of FAP (FAPI). Therefore, this retrospective study aimed to evaluate the role of the novel hybrid imaging probe for sarcomas as a first clinical evaluation. Methods A cohort of 15 patients underwent 68Ga-FAPI-PET/CT for staging or restaging. The acquisition of PET scans was performed 60 min after administration of 127 to 308 MBq of the tracer. The uptake of 68Ga-FAPI in malignant tissue as well as in healthy organs was quantified by standardized uptake values SUVmean and SUVmax. Results Excellent tumor-to-background ratios (> 7) could be achieved due to low background activity and high SUVmax in primary tumors (median 7.16), local relapses (median 11.47), and metastases (median 6.29). The highest uptake was found for liposarcomas and high-grade disease (range 18.86–33.61). A high SUVmax (> 10) was observed for clinically more aggressive disease. Conclusion These preliminary findings suggest a high potential for the clinical use of 68Ga-FAPI-PET/CT for patients diagnosed with sarcoma.

Role of Functional Imaging in the Management of Lymphoma

2011 ◽  
Vol 29 (14) ◽  
pp. 1844-1854 ◽  
Author(s):  
Bruce D. Cheson
Keyword(s):  
Fdg Pet ◽  
B Cell Lymphoma ◽  
Post Treatment ◽  
Metabolic Imaging ◽  
Interim Pet ◽  
Positron Emission ◽  
Pet Ct ◽  
Pretreatment Assessment ◽  
Pet Scans

18-F-fluorodeoxyglucose (FDG) –positron emission tomography (PET), and more recently PET/computed tomography (CT), is the most sensitive and specific imaging technique currently available for patients with lymphoma. Nevertheless, despite being increasingly used in pretreatment assessment, midtreatment evaluation of response, post-treatment restaging, and surveillance during follow-up of patients with lymphoma, its impact on clinical outcome in most clinical situations remains to be confirmed. PET/CT provides its greatest clinical benefit in the post-treatment evaluation of Hodgkin's lymphoma and diffuse large B-cell lymphoma; however, the role of metabolic imaging in other indications and in other histologies remains to be demonstrated. Ongoing risk-adapted studies will hopefully provide evidence for clinical improvement on the basis of altering treatment as a result of interim PET results. Efforts are ongoing to better standardize the conduct and interpretation of FDG-PET scans. FDG-PET has the potential to improve lymphoma patient management; however, its usefulness will likely vary by histology, stage, therapy, and clinical setting.

scholarly journals The role of type II transmembrane serine protease-mediated signaling in cancer

FEBS Journal ◽  
2016 ◽  
Vol 284 (10) ◽  
pp. 1421-1436 ◽  
Author(s):  
Lauren M. Tanabe ◽  
Karin List
Keyword(s):  
Serine Protease ◽  
Type Ii ◽  
Transmembrane Serine Protease

scholarly journals TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 384
Author(s):  
Mai Kishimoto ◽  
Kentaro Uemura ◽  
Takao Sanaki ◽  
Akihiko Sato ◽  
William W. Hall ◽  
...  
Keyword(s):  
Viral Entry ◽  
Vaccine Development ◽  
Spike Protein ◽  
Tissue Tropism ◽  
Type Ii ◽  
Angiotensin Converting Enzyme 2 ◽  
Exogenous Expression ◽  
Transmembrane Serine Protease ◽  
The Impact

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes host proteases, including a plasma membrane-associated transmembrane protease, serine 2 (TMPRSS2) to cleave and activate the virus spike protein to facilitate cellular entry. Although TMPRSS2 is a well-characterized type II transmembrane serine protease (TTSP), the role of other TTSPs on the replication of SARS-CoV-2 remains to be elucidated. Here, we have screened 12 TTSPs using human angiotensin-converting enzyme 2-expressing HEK293T (293T-ACE2) cells and Vero E6 cells and demonstrated that exogenous expression of TMPRSS11D and TMPRSS13 enhanced cellular uptake and subsequent replication of SARS-CoV-2. In addition, SARS-CoV-1 and SARS-CoV-2 share the same TTSPs in the viral entry process. Our study demonstrates the impact of host TTSPs on infection of SARS-CoV-2, which may have implications for cell and tissue tropism, for pathogenicity, and potentially for vaccine development.

scholarly journals Potent and specific inhibition of the biological activity of the type-II transmembrane serine protease matriptase by the cyclic microprotein MCoTI-II

2014 ◽  
Vol 112 (08) ◽  
pp. 402-411 ◽  
Author(s):  
Kelly Gray ◽  
Salma Elghadban ◽  
Panumart Thongyoo ◽  
Kate A. Owen ◽  
Roman Szabo ◽  
...  
Keyword(s):  
Serine Protease ◽  
Biological Effects ◽  
Type Ii ◽  
Proteolytic Activation ◽  
Epithelial Barrier Function ◽  
Epithelial Homeostasis ◽  
Starting Point ◽  
Momordica Cochinchinensis ◽  
Transmembrane Serine Protease

SummaryMatriptase is a type-II transmembrane serine protease involved in epithelial homeostasis in both health and disease, and is implicated in the development and progression of a variety of cancers. Matriptase mediates its biological effects both via as yet undefined substrates and pathways, and also by proteolytic cleavage of a variety of well-defined protein substrates, several of which it shares with the closely-related protease hepsin. Development of targeted therapeutic strategies will require discrimination between these proteases. Here we have investigated cyclic microproteins of the squash Momordica cochinchinensis trypsin-inhibitor family (generated by total chemical synthesis) and found MCoTI-II to be a high-affinity (Ki 9 nM) and highly selective (> 1,000-fold) inhibitor of matriptase. MCoTI-II efficiently inhibited the proteolytic activation of pro-hepatocyte growth factor (HGF) by matriptase but not by hepsin, in both purified and cell-based systems, and inhibited HGF-dependent cell scattering. MCoTI-II also selectively inhibited the invasion of matriptase-expressing prostate cancer cells. Using a model of epithelial cell tight junction assembly, we also found that MCoTI-II could effectively inhibit the re-establishment of tight junctions and epithelial barrier function in MDCK-I cells after disruption, consistent with the role of matriptase in regulating epithelial integrity. Surprisingly, MCoTI-II was unable to inhibit matriptase-dependent proteolytic activation of prostasin, a GPI-anchored serine protease also implicated in epithelial homeostasis. These observations suggest that the unusually high selectivity afforded by MCoTI-II and its biological effectiveness might represent a useful starting point for the development of therapeutic inhibitors, and further highlight the role of matriptase in epithelial maintenance.

scholarly journals Essential Role of Endocytosis of the Type II Transmembrane Serine Protease TMPRSS6 in Regulating Its Functionality

2011 ◽  
Vol 286 (33) ◽  
pp. 29035-29043 ◽  
Author(s):  
François Béliveau ◽  
Cédric Brulé ◽  
Antoine Désilets ◽  
Brandon Zimmerman ◽  
Stéphane A. Laporte ◽  
...  
Keyword(s):  
Serine Protease ◽  
Essential Role ◽  
Type Ii ◽  
Transmembrane Serine Protease

scholarly journals Increased uptake of 68Ga-DOTA-FAPI-04 in bones and joints: metastases and beyond

2021 ◽  
Author(s):  
Chunxia Qin ◽  
Yangmeihui Song ◽  
Xi Liu ◽  
Yongkang Gai ◽  
Qingyao Liu ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Bone Diseases ◽  
Bone Lesions ◽  
Benign Lesions ◽  
Osteofibrous Dysplasia ◽  
Benign Diseases ◽  
Pet Ct ◽  
Malignant Lesions ◽  
The Mean

Abstract Purpose: To describe the uptake of 68Gallium-labelled fibroblast activation protein inhibitor (68Ga-FAPI) in bones and joints for better understanding of the role of 68Ga-FAPI PET in benign and malignant bone lesions and joint diseases. Methods: All 129 68Ga-FAPI PET/MR or PET/CT scans from June 1, 2020 to February 20, 2021 performed at our PET centre were retrospectively reviewed. Foci of elevated 68Ga-FAPI uptake in bones and joints were identified. All lesions were divided into malignant and benign disease. Benign lesions included osteofibrous dysplasia, periodontitis, degenerative bone diseases, arthritis, and other inflammatory or trauma-related abnormalities. The number, locations and SUVmax of all lesions were recorded and analysed. Results: Elevated uptake of 68Ga-FAPI in/around bones and joints were found in 82 cases (63.57%). A total of 295 lesions were identified, including 94 (31.9%) malignant lesions (all were metastases) and 201 (68.1%) benign lesions. The benign lesions consisted of 13 osteofibrous dysplasia, 48 degenerative bone disease, 33 periodontitis, 56 arthritis, and 51 other inflammatory or trauma-related abnormalities. Spine, shoulder joint, alveolar ridge, and pelvis were the most commonly involved locations. Bone metastases were mainly distributed in the spine, pelvis and ribs. Among benign diseases, periodontitis and arthritis are site-specific. The mean SUVmax of bone metastases was significantly higher than that of benign diseases (7.14 ± 4.33 vs. 3.57 ± 1.60, p < 0.0001), but overlap existed. The differences in SUVmax among subgroups of benign diseases were statistically significant (p < 0.0001), with much higher uptake in periodontitis (4.45 ± 1.17). Conclusion: 68Ga-FAPI accumulated in both bone metastases and some benign diseases of bones and joints. Although the uptake of 68Ga-FAPI was often higher in bone metastases, this finding cannot be used to distinguish between benign and malignant lesions.

Comparison of Fluorine(18)-fluorodeoxyglucose and Gallium(68)-citrate PET/CT in patients with tuberculosis

2019 ◽  
Vol 58 (05) ◽  
pp. 371-378
Author(s):  
Alfred O. Ankrah ◽  
Ismaheel O. Lawal ◽  
Tebatso M.G. Boshomane ◽  
Hans C. Klein ◽  
Thomas Ebenhan ◽  
...  
Keyword(s):  
Tracer Uptake ◽  
Pet Ct ◽  
The Mean ◽  
18F Fdg ◽  
Definition Of ◽  
Gallium 68 ◽  
Attending Physician ◽  
Pet Scans ◽  
The Brain

Abstract 18F-FDG and 68Ga-citrate PET/CT have both been shown to be useful in the management of tuberculosis (TB). We compared the abnormal PET findings of 18F-FDG- and 68Ga-citrate-PET/CT in patients with TB. Methods Patients with TB on anti-TB therapy were included. Patients had a set of PET scans consisting of both 18F-FDG and 68Ga-citrate. Abnormal lesions were identified, and the two sets of scans were compared. The scan findings were correlated to the clinical data as provided by the attending physician. Results 46 PET/CT scans were performed in 18 patients, 11 (61 %) were female, and the mean age was 35.7 ± 13.5 years. Five patients also had both studies for follow-up reasons during the use of anti-TB therapy. Thirteen patients were co-infected with HIV. 18F-FDG detected more lesions than 68Ga-citrate (261 vs. 166, p < 0.0001). 68Ga-citrate showed a better definition of intracerebral lesions due to the absence of tracer uptake in the brain. The mean SUVmax was higher for 18F-FDG compared to 68Ga-citrate (5.73 vs. 3.01, p < 0.0001). We found a significant correlation between the SUVmax of lesions that were determined by both tracers (r = 0.4968, p < 0.0001). Conclusion Preliminary data shows 18F-FDG-PET detects more abnormal lesions in TB compared to 68Ga-citrate. However, 68Ga-citrate has better lesion definition in the brain and is therefore especially useful when intracranial TB is suspected.

Role of hyperglucagonemia in maintenance of increased rates of hepatic glucose output in type II diabetics

Diabetes ◽  
1987 ◽  
Vol 36 (3) ◽  
pp. 274-283 ◽  
Author(s):  
A. D. Baron ◽  
L. Schaeffer ◽  
P. Shragg ◽  
O. G. Kolterman
Keyword(s):  
Type Ii ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Type Ii Diabetics ◽  
Glucose Output

Role of lipid oxidation in pathogenesis of insulin resistance of obesity and type II diabetes

Diabetes ◽  
1987 ◽  
Vol 36 (11) ◽  
pp. 1341-1350 ◽  
Author(s):  
J. P. Felber ◽  
E. Ferrannini ◽  
A. Golay ◽  
H. U. Meyer ◽  
D. Theibaud ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Oxidation ◽  
Type Ii Diabetes ◽  
Type Ii
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