Preparation and bioevaluation of 99mTc-HYNIC-annexin B1 as a novel radioligand for apoptosis imaging |
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Authors: | Quan-Yong Luo Fang Wang Zhi-Yong Zhang Yi Zhang Han-Kui Lu Shu-Han Sun Rui-Sen Zhu |
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Institution: | (1) Department of Nuclear Medicine, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai, 200233, China;(2) Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China;(3) Radiopharmaceutical Lab, Shanghai GMS Pharmaceutical Co., Ltd., Shanghai, 201108, China |
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Abstract: | Annexin B1, a novel Ca2+-dependent PS-binding protein, has been shown to have a high affinity for PS exposed on the surface of apoptotic cells. To
develop and bioevaluate an annexin B1 based PS-targeting radiotracer, annexin B1 was radiolabeled with 99mTc using HYNIC as a bifunctional chelator. Binding assays with activated platelets and apoptotic SP2/0 cells were carried
out to evaluate the in vitro biological activity of 99mTc-HYNIC-annexin B1. Biodistribution of this radioligand was studied in normal mice. Dexamethasone-induced murine thymus apoptosis
and fas-mediated murine liver apoptosis models were used to investigate the ability of radiolabeled annexin B1 to detect apoptosis
in vivo. The labeling procedure yielded a compound with up to 98% radiochemical purity and good in vitro stability. The in vitro
binding assays indicated that 99mTc-HYNIC-annexin B1 retain its PS-binding activity. Biodistribution of the compound in mice showed that 99mTc-HYNIC-annexin B1 is rapidly cleared from the blood and predominantly accumulates in the kidney. The marked increase in
dexamethasone-treated murine thymus uptake and fas-mediated murine liver uptake correlated with histologic evidence of apoptosis.
These data suggested that 99mTc-HYNIC-annexin B1 retain its in vitro and in vivo biological activities. This radiotracer may therefore be useful as a novel
radioligand for the noninvasive detecting of PS externalization associated with apoptosis. |
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Keywords: | Apoptosis Molecular imaging Radiopharmaceuticals Annexin |
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