Development of a novel, fibrin‐specific PET tracer

Abstract

Fibrin deposition is observed in several diseases such as atherosclerosis, deep vein thrombosis, and also tumors, where it contributes to the formation of mature tumor stroma. The aim of this study was to develop a gallium-labeled peptide tracer on the basis of the fibrin-targeting peptide Epep for PET imaging of fibrin deposition. For this purpose, the peptide Epep was modified with a NOTA moiety for radiolabeling with Ga and Ga and compared with the earlier validated In-DOTA-Epep tracer. In vitro binding assays of Ga-NOTA-Epep displayed an enhanced retention as compared to previously published data showing binding of In-DOTA-Epep to human (84.0 ± 0.6 vs 66.6 ± 1.4 %Dose) and mouse derived fibrin clots (83.5 ± 1.7 vs 74.2 ± 2.4% Dose). In vivo blood kinetics displayed a bi-phasic elimination profile (t , = 2.6 ± 1.0 minutes and t , = 15.8 ± 1.3 minutes) and ex vivo biodistribution showed low blood values at 4 hours post injection and a low uptake in nontarget tissue (<0.2 %ID/g; kidneys, 1.9%ID/g). In conclusion, taking into account the ease of radiolabeling and the promising in vitro and in vivo studies, gallium-labeled Epep displays the potential for further development towards a PET tracer for fibrin deposition.

The Role of von Willebrand Factor in Vascular Inflammation: From Pathogenesis to Targeted Therapy

“…Plasma level of VWF is determined by both genetic [14, 15] and nongenetic factors, such as ABO blood group, aging, and sexual hormones (i.e., estrogens). Endothelial dysfunction and activation, vascular aging, and arterial stiffness are all associated with increased levels of VWF [16, 17]. Nitric oxide (NO), a marker of endothelial health, exerts an inhibitory effect on VWF release by ECs, probably blocking the granule membrane fusion process or inhibiting calcium mobilization from WPBs [15, 18, 19].…”

Biomaterials to model and measure epithelial cancers

“…Antigen-binding fragment (Fab) probes can be combined with a radioisotope to image fibrin clots in the tumour microenvironment 127 . Such probes also demonstrate low retention times in non-target tissue in vivo 126,128 . Fibronectin is also overexpressed during EMT, making it a prime target for early cancer detection probes 124,129–131 .…”