(68)Ga-Labeled Maleimide for Blood Pool and Lymph PET Imaging through Covalent Bonding to Serum Albumin In Vivo

[Image: see text] This study aims to develop a novel (68)Ga-labeled tracer, which can covalently bind to albumin in vivo based on the maleimide–thiol strategy, and to evaluate its potential applications using positron emission tomography (PET). (68)Ga-labeled maleimide-monoamide-DOTA (denoted as [(68)Ga]Ga-DM) was prepared conveniently with a high radiochemical yield (>90%) and radiochemical purity (>99%). Its molar activity was calculated as 249.60 ± 68.50 GBq/μmol, and the octanol–water partition coefficient (LogP) was −3.15 ± 0.08 with good stabilities. In vitro experiments showed that [(68)Ga]Ga-DM can bind to albumin efficiently and rapidly, with a binding fraction of over 70%. High uptake and excellent retention in blood were observed with a long half-life (t(1/2Z)) of 190.15 ± 24.14 min, which makes it possible for blood pool PET imaging with high contrast. The transient micro-bleeding in the rat model was detected successfully with PET imaging. In addition, the uptakes of [(68)Ga]Ga-DM in the inflammatory popliteal lymph nodes depend on the severity (5.90% ID/g and 2.32% ID/g vs 1.01% ID/g for healthy lymph nodes at 0.5 h post-injection) indicating its feasibility for lymphatic imaging. In conclusion, a novel (68)Ga-labeled tracer was prepared with high efficiency and yield in mild conditions. Based on the promising properties of bonding covalently to albumin, great stability, high blood contrast with a long half-life, and well environmental tolerance, [(68)Ga]Ga-DM could be developed as a potential tracer for PET imaging of blood pool, bleeding, and vascular permeability alteration diseases in the clinic.