title: Preparation and bioevaluation of (99m)Tc-HYNIC-annexin B1 as a novel radioligand for apoptosis imaging.
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 (99m)Tc 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 (99m)Tc-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 (99m)Tc-HYNIC-annexin B1 retain its PS-binding activity. Biodistribution of the compound in mice showed that (99m)Tc-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 (99m)Tc-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.
authors.affiliation: Department of Nuclear Medicine, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233, China. lqyn@sh163.net
authors.forename: Quan-Yong
authors.initials: QY
authors.lastname: Luo
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Han-Kui
authors.initials: HK
authors.lastname: Lu
authors.forename: Shu-Han
authors.initials: SH
authors.lastname: Sun
authors.forename: Rui-Sen
authors.initials: RS
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017302:Annexins / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000166:cytology*; D008024:Ligands; D008099:Liver / Q000166:cytology*; D051379:Mice; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D010718:Phosphatidylserines / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D017302:Annexins; D053222:Fas Ligand Protein; D008024:Ligands; D015609:Organotechnetium Compounds; D010718:Phosphatidylserines; C530012:technetium 99m HYNIC-annexin B1; D003907:Dexamethasone