CC49单链抗体片段-链霉亲和素融合蛋白预靶向的149钷、166钬和177镥-多胺基多羧基-生物素在荷瘤裸鼠中的生物学比较

Biological comparison of 149Pm-, 166Ho-, and 177Lu-DOTA-biotin pretargeted by CC49 scFv-streptavidin fusion protein in xenograft-bearing nude mice.

作者信息

Lewis Michael R, Zhang Jiuli, Jia Fang, Owen Nellie K, Cutler Cathy S, Embree Mary F, Schultz Jody, Theodore Louis J, Ketring Alan R, Jurisson Silvia S, Axworthy Donald B

机构信息

Department of Veterinary Medicine and Surgery, University of Missouri-Columbia, Columbia, MO 65211, USA.

出版信息

Nucl Med Biol. 2004 Feb;31(2):213-23. doi: 10.1016/j.nucmedbio.2003.08.004.

DOI:10.1016/j.nucmedbio.2003.08.004

PMID:15013487

Abstract

The radiolanthanides (149)Pm, (166)Ho, and (177)Lu possess a range of half-lives and alpha(-) beta(-) energies for targeted radiotherapy of cancer. (149)Pm-, (166)Ho-, and (177)Lu-DOTA-biotin were pretargeted to LS174T colorectal tumors in nude mice with CC49 scFvSA antibody-streptavidin fusion protein. Tumor uptakes of (149)Pm (22.9% ID/g), (166)Ho (30.2% ID/g), and (177)Lu (35.4% ID/g) peaked at 1-4 h. Rapid blood disappearance was accompanied by urinary excretion of 59-66% ID within 1 h. Biodistributions of these agents show promise for pretargeted radioimmunotherapy of cancer.

摘要

放射性镧系元素（149）钷、（166）钬和（177）镥具有一系列半衰期和α、β能量，可用于癌症的靶向放射治疗。用CC49单链抗体片段-链霉亲和素融合蛋白将（149）钷、（166）钬和（177）镥-二氧四氮杂环十二烷-生物素预靶向裸鼠的LS174T结肠直肠肿瘤。（149）钷（22.9%注射剂量/克）、（166）钬（30.2%注射剂量/克）和（177）镥（35.4%注射剂量/克）的肿瘤摄取在1-4小时达到峰值。血液快速清除，1小时内尿液排泄量为注射剂量的59-66%。这些药物的生物分布显示出在癌症预靶向放射免疫治疗方面的前景。