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学科主题: 公共卫生
题名:
Blood Clearance Kinetics, Biodistribution, and Radiation Dosimetry of a Kit-Formulated Integrin alpha(v)beta(3)-Selective Radiotracer Tc-99m-3PRGD(2) in Non-Human Primates
作者: Jia, Bing2,3; Liu, Zhaofei2,3; Zhu, Zhaohui4; Shi, Jiyun2,3; Jin, Xiaona4; Zhao, Huiyun2; Li, Fang4; Liu, Shuang1; Wang, Fan2,3
关键词: Integrin alpha(v)beta(3) ; Tc-99m-labeled cyclic RGD peptides ; Biodistribution ; Dosimetry ; Primates
刊名: MOLECULAR IMAGING AND BIOLOGY
发表日期: 2011-08-01
DOI: 10.1007/s11307-010-0385-y
卷: 13, 期:4, 页:730-736
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Radiology, Nuclear Medicine & Medical Imaging
研究领域[WOS]: Radiology, Nuclear Medicine & Medical Imaging
关键词[WOS]: POSITRON-EMISSION-TOMOGRAPHY ; TUMOR ANGIOGENESIS ; CANCER-PATIENTS ; PEG(4) LINKERS ; PHARMACOKINETICS ; EXPRESSION ; DIMERS
英文摘要:

Tc-99m-3PRGD(2) is a Tc-99m-labeled dimeric cyclic RGD peptide with increased receptor binding affinity and improved kinetics for in vivo imaging of integrin alpha(v)beta(3) expression in nude mouse model. To accelerate its clinical translation, we reported here the evaluation of the kit-formulated Tc-99m-3PRGD(2) in healthy cynomolgus primates for its blood clearance kinetics, biodistribution, and radiation dosimetry.

Healthy cynomolgus primates (4.1 +/- 0.7 kg, n = 5) were anesthetized, and the venous blood samples were collected via a femoral vein catheter at various time points after injection of similar to 555 MBq of Tc-99m-3PRGD(2). Serial whole-body scans were performed with a dual-head single photon emission computed tomography system after administering similar to 555 MBq of Tc-99m-3PRGD(2) in the non-human primates, and the radiation dosimetry estimate was calculated.

Tc-99m-3PRGD(2) could be easily obtained from freeze-dried kits with high radiochemical purity (> 95%) and high specific activity (similar to 5 Ci/mu mol). Tc-99m-3PRGD(2) had a rapid blood clearance with less than 1% of the initial radioactivity remaining in the blood circulation at 60 min postinjection. No adverse reactions were observed up to 4 weeks after the repeated dosing. The whole-body images exhibited high kidney uptake of Tc-99m-3PRGD(2) and high radioactivity accumulation in the bladder, demonstrating the rapid renal clearance of this tracer. The highest radiation doses of Tc-99m-3PRGD(2) were found in the kidneys (13.2 +/- 1.08 mu Gy/MBq) and the bladder wall (33.1 +/- 1.91 mu Gy/MBq).

Tc-99m-3PRGD(2) can be readily available using the kit formulation. This tracer is safe and well tolerated, and no adverse events occurred in non-human primates. Further clinical testing and translation of Tc-99m-3PRGD(2) for noninvasive imaging of integrin alpha(v)beta(3) in humans are warranted.

语种: 英语
所属项目编号: 30870728 ; 20820102035 ; 30930030 ; 30900373 ; 2007AA02Z467 ; 2009ZX09103-733 ; 2009ZX09103-746 ; 2009ZX09301-010
项目资助者: NSFC ; "863" project ; Ministry of Science and Technology of China
WOS记录号: WOS:000292310000014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64868
Appears in Collections:北京大学医药卫生分析中心_期刊论文

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作者单位: 1.Purdue Univ, Sch Hlth Sci, W Lafayette, IN 47907 USA
2.Peking Univ, Med Isotopes Res Ctr, Beijing 100191, Peoples R China
3.Peking Univ, Sch Basic Med Sci, Dept Radiat Med, Beijing 100191, Peoples R China
4.Peking Union Med Coll, Dept Nucl Med, Beijing 100730, Peoples R China

Recommended Citation:
Jia, Bing,Liu, Zhaofei,Zhu, Zhaohui,et al. Blood Clearance Kinetics, Biodistribution, and Radiation Dosimetry of a Kit-Formulated Integrin alpha(v)beta(3)-Selective Radiotracer Tc-99m-3PRGD(2) in Non-Human Primates[J]. MOLECULAR IMAGING AND BIOLOGY,2011,13(4):730-736.
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