ABSTRACT
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 protein was selected, and the C-terminal of the protein was modified by sulfonation and coupled to the bifunctional 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 imaging 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. lts 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 SUV max 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.
ABSTRACT
Objective:To automatically synthesize Al 18F-fibroblast activation protein inhibitor (FAPI)-74, and explore its value of clinical application. Methods:Al 18F-FAPI-74 was synthesized automatically by the commercial synthesis module CFN-MPS-100, and its yield, radiochemical purity and stability were determined. Sixteen normal Kunming (KM) mice were randomly divided into 4 groups and euthanized at 10, 30, 60 and 90 min after Al 18F-FAPI-74 injection, and the biodistribution was measured. MicroPET/CT dynamic scanning (60 min) was performed in 5 rat pancreatic tumor-bearing BALB/c nude mice to observe the tumor uptake. Al 18F-FAPI-74 PET/CT imaging was performed on 3 volunteers (1 male, 2 females; age: 37, 41, 43 years) to evaluate the clinical application value of Al 18F-FAPI-74. Results:The automated synthesis time of Al 18F-FAPI-74 was about 35 min, with the synthesis yield of (21.34±3.86)% (without attenuation correction, n=5) and the radiochemical purity more than 99%. The radiochemical purity was still more than 96% after placement at 37 ℃ for 6 h. Biodistribution in normal mice and microPET/CT dynamic scanning in tumor-bearing nude mice showed that consistently high uptake in the kidneys and bladder, and the tumor uptake was the highest at 20 min, and the maximum tumor-to-muscle ratio was 3.16±0.01 at 60 min. PET/CT imaging on volunteers showed that there was a small amount of uptake in myocardium, most organs such as the liver and lung had background uptake, and the maximum SUV max of persistent high uptake of tumor was 17.08. Conclusions:Al 18F-FAPI-74 has the advantages of simple synthesis, high yield, stable quality and good imaging performance in mice and volunteers. It is a kind of imaging agent that meets the requirements of clinical diagnosis.