Designing Tracers for PET Imaging of the Urokinase-type Plasminogen Activator Receptor from a Cyclic uPA-derived Peptide - First in Vitro Evaluations.

08:00 EDT 10th April 2019 | BioPortfolio

Summary of "Designing Tracers for PET Imaging of the Urokinase-type Plasminogen Activator Receptor from a Cyclic uPA-derived Peptide - First in Vitro Evaluations."

The treatment of cancer remains a major challenge, especially after tumour cell dissemination and metastases formation. Expression of the urokinase-type plasminogen activation system including urokinase (uPA) and its receptor (uPAR) has been associated with the complex process of cell migration, a tumour's invasive potential as well as a reduced overall- and disease-free survival of patients with solid cancers and haematological disorders. A cyclic peptide cyclo[21,29][d-Cys ,Cys ]-uPA was designed from the growth factor-like domain (GFD) of urokinase whose binding to uPAR was found to inhibit tumour growth and spread of human ovarian cancer cells in mice. With the aim of visualising uPAR expression using PET imaging to attempt an estimate on the tumour's aggressiveness, the cyclic peptide was modified with an either C- or N-terminally attached variable spacer and chelator. The free ligands were evaluated for their binding affinities to the isolated human uPAR and labelled with Ga and Lu to assess their lipophilicities and stabilities in human serum. Although retaining the full binding potential displayed by cyclo[21,29][d-Cys ,Cys ]-uPA to its target was found to be a challenging task upon both C- and N-terminal modification, chelator-bearing ligands were identified that can serve as promising starting points in the development of uPAR-addressing PET tracers.


Journal Details

This article was published in the following journal.

Name: Journal of labelled compounds & radiopharmaceuticals
ISSN: 1099-1344


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Medical and Biotech [MESH] Definitions

An extracellular receptor specific for UROKINASE-TYPE PLASMINOGEN ACTIVATOR. It is attached to the cell membrane via a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE and plays a role in the co-localization of urokinase-type plasminogen activator with PLASMINOGEN.

A proteolytic enzyme in the serine protease family found in many tissues which converts PLASMINOGEN to FIBRINOLYSIN. It has fibrin-binding activity and is immunologically different from UROKINASE-TYPE PLASMINOGEN ACTIVATOR. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases.

A member of the serpin family of proteins. It inhibits both the tissue-type and urokinase-type plasminogen activators.

Member of the serpin family of proteins. It inhibits both the tissue-type and urokinase-type plasminogen activators.

An acylated inactive complex of streptokinase and human lysine-plasminogen. After injection, the acyl group is slowly hydrolyzed, producing an activator that converts plasminogen to plasmin, thereby initiating fibrinolysis. Its half-life is about 90 minutes compared to 5 minutes for TPA; (TISSUE PLASMINOGEN ACTIVATOR); 16 minutes for UROKINASE-TYPE PLASMINOGEN ACTIVATOR and 23 minutes for STREPTOKINASE. If treatment is initiated within 3 hours of onset of symptoms for acute myocardial infarction, the drug preserves myocardial tissue and left ventricular function and increases coronary artery patency. Bleeding complications are similar to other thrombolytic agents.

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