Development of a novel, fibrin-specific PET tracer.
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 with67Ga and68Ga and compared with the earlier validated111In-DOTA-Epep tracer. In vitro binding assays of67Ga-NOTA-Epep displayed an enhanced retention as compared to previously published data showing binding of111In-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.
Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Tiemen R
0000-0001-8393-1369
TR
van Mourik
Department of Nuclear Medicine, University of Münster, Münster, Germany.
Michael
M
Claesener
Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Klaas
K
Nicolay
Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.|Department of Oncology Solutions, Philips Research, Eindhoven, The Netherlands.
Holger
H
Grüll
D000818:Animals; D015195:Drug Design; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring; D051379:Mice; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011849:Radioactive Tracers
D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D010455:Peptides; D011849:Radioactive Tracers; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D005337:Fibrin
Epep; NOTA; PET imaging; fibrin; gallium