Synthesis and biological evaluation of 68Ga-NOTA-CD44:a novel tracer targeting atherosclerotic plaques
Objective To construct 68Ga-1,4,7-trizacyclononane-1,4,7-triacetic acid(NOTA)-CD44 as a novel atherosclerosis tracer targeting hyaluronic acid(HA),and evaluate its biological property and molecular imaging features.Methods Low molecular weight(LMW)recombinant human CD44 pro-tein was selected,and the C-terminal of the protein was modified by sulfonation and coupled to the bifunc-tional ligand NOTA to synthesize a novel molecular probe 68Ga-NOTA-CD44 targeting HA.The biological properties of the probe,such as labeling rate and in vitro stability,were studied.Three atherosclerotic plaque model mice and three normal C57BL/6 mice were studied by 68Ga-NOTA-CD44 microPET/CT ima-ging and pathological examination.Results 68Ga-NOTA-CD44 tracer was synthesized and purified with the radiochemical purity above 99％,and the specific activity was up to 62.22 MBq/nmol.Its stability was good in PBS,and the radiochemical purity was over 90％after incubation for 3 h.After intravenous injection,the probe was metabolized mainly by the kidneys,and its metabolic level decreased successively in the liver,lungs and blood.MicroPET/CT imaging results of atherosclerotic model mice suggested that the uptake in the plaque of abdominal aorta was higher at 60 min after injection,with SUVmax and target/background ratio(TBR)max of 1.14±0.02 and 4.95±0.93,and the probe had certain atherosclerotic plaque eroded targeting,which was consistent with the pathological result.Conclusions As a novel probe,68Ga-NOTA-CD44 is simple to prepare and has a high labeling rate.It has good physicochemical properties and in vivo biological properties,and can display atherosclerotic eroded plaques sensitively.68Ga-NOTA-CD44 has a promising prospect to be a new molecular probe for early noninvasive recognition of atherosclerotic eroded plaques.
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