The in vitro performance of some of the new tetrazine probes turned out to be comparable to the established lead probe [Lu]Lu-DOTA-PEG-Tz ([Lu]4). However, tumor pretargeting studies in vivo showed lower tumor uptake and increased uptake in non-target organs.
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.
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