Development of a novel, fibrin‐specific PET tracer. (30th May 2017)

• Record Type: Journal Article
• Authors: van Mourik, Tiemen R.; Claesener, Michael; Nicolay, Klaas; Grüll, Holger
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 60:Number 6(2017)
• Page Start: 286
• Page End: 293
• Publication Date: 2017-05-30
• Subjects: Epep -- fibrin -- gallium -- NOTA -- PET imaging; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3501
• Languages: English
• ISSNs: 0362-4803

Abstract

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 67 Ga and 68 Ga and compared with the earlier validated 111 In‐DOTA‐Epep tracer. In vitro binding assays of 67 Ga‐NOTA‐Epep displayed an enhanced retention as compared to previously published data showing binding of 111 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 (t1/2, α = 2.6 ± 1.0 minutes and t1/2, β = 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. Abstract : In this study, we investigated the potential of the fibrin‐binding peptide Epep as a PET tracer for fibrin deposition. In vitro binding studies of Ga(III)‐labeled NOTA‐Epep displayed an enhanced retention towards human‐ and mouse‐derived fibrin clots. Ex vivo biodistribution showed low blood values at 4 hours postinjection and a low uptake in nontarget tissue. Together with the ease of 68 Ga labeling and the favorable in vivo characteristics of 67 Ga‐NOTA‐Epep, this peptide displays a promising role for clinical translation.