Hashmi M, Rosebrough S F
Visus Pharmaceuticals, Inc., Department of Radiology, University of Rochester Medical Center, NY 14642, USA.
Drug Metab Dispos. 1995 Dec;23(12):1362-7.
The exceptionally high affinity of streptavidin for biotin may be exploited for two-step in vivo approaches for delivering radiolabelled biotin derivatives to lesion-bound streptavidin-conjugated monoclonal antibodies. A radiolabeled biotin derivative was prepared, and its characterization, stability, pharmacokinetics, and biodistribution studies are presented. This derivative contains deferoxamine, a chelating moiety with high affinity for trivalent metals suitable for imaging and therapy. Deferoxamineacetyl-cysteinylbiotin (DACB) was synthesized in three steps: nucleophilic reaction of deferoxamine with N-hydroxysuccinimide iodoacetate, aminolysis of N-hydroxysuccinimide biotin by L-cysteine, followed by coupling of cysteinylbiotin with N-iodoacetyldeferoxamine. DACB was characterized by matrix-assisted laser desorption/ionization MS. Radiolabeling of DACB with 67Ga led to a labeling efficiency of > 95%. Pharmacokinetics of 67Ga DACB exhibited rapid blood clearance, with < 10% circulating at 30 min and < 1% at 6 hr. Plasma samples collected at various time intervals showed > 95% binding with streptavidin, indicating in vivo stability of 67Ga DACB. Urinalysis showed > 80% of the administered dose excreted at 6 hr. Biodistribution data at 6 hr showed < 1% radioactivity remaining per organ.
链霉亲和素与生物素之间极高的亲和力可用于两步体内方法，将放射性标记的生物素衍生物递送至与病变结合的链霉亲和素偶联单克隆抗体。制备了一种放射性标记的生物素衍生物，并介绍了其表征、稳定性、药代动力学和生物分布研究。该衍生物含有去铁胺，这是一种对三价金属具有高亲和力的螯合部分，适用于成像和治疗。去铁胺乙酰半胱氨酰生物素（DACB）通过三步合成：去铁胺与N-羟基琥珀酰亚胺碘乙酸酯的亲核反应，L-半胱氨酸对N-羟基琥珀酰亚胺生物素的氨解，然后半胱氨酰生物素与N-碘乙酰去铁胺偶联。DACB通过基质辅助激光解吸/电离质谱进行表征。用67Ga对DACB进行放射性标记，标记效率>95%。67Ga DACB的药代动力学表现为血液快速清除，30分钟时循环量<10%，6小时时<1%。在不同时间间隔收集的血浆样本显示与链霉亲和素的结合率>95%，表明67Ga DACB在体内的稳定性。尿液分析显示，6小时时排出的给药剂量>80%。6小时时的生物分布数据显示，每个器官剩余的放射性<1%。
