Synthesis and biological evaluation of 68Ga-NOTA-CD44: a novel tracer targeting atherosclerotic plaques
10.3760/cma.j.cn321828-20230206-00029
- VernacularTitle:新型动脉粥样硬化斑块示踪剂 68Ga－NOTA－CD44的制备与生物学评价
- Author:
Bo WANG
1
;
Li LI
;
Xue YU
;
Chuxin ZHANG
;
Min YAN
;
Huiling LI
;
Huibin RU
;
Ping WU
;
Ruonan WANG
;
Zhifang WU
;
Sijin LI
Author Information
1. 山西医科大学第一医院核医学科、分子影像精准诊疗省部共建协同创新中心，太原 030001
- Keywords:
Plaque, atherosclerotic;
Antigens, CD44;
Isotope labeling;
Gallium radioisotopes;
Mice
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2024;44(2):104-108
- CountryChina
- Language:Chinese
-
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.
