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学科主题: 公共卫生
题名:
(TcO)-Tc-99m(MAG(2)-3G(3)-dimer): a new integrin alpha(v)beta(3)-targeted SPECT radiotracer with high tumor uptake and favorable pharmacokinetics
作者: Shi, Jiyun1,2; Wang, Lijun1; Kim, Young-Seung1; Zhai, Shizhen1; Jia, Bing2; Wang, Fan2; Liu, Shuang1
关键词: Integrin alpha(v)beta(3) ; Tc-99m-labeled cyclic RGD peptides ; Tumor imaging
刊名: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
发表日期: 2009-11-01
DOI: 10.1007/s00259-009-1166-1
卷: 36, 期:11, 页:1874-1884
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]: CYCLIC RGDFK DIMER ; POSITRON-EMISSION-TOMOGRAPHY ; GLIOMA INTEGRIN-ALPHA(V)BETA(3) EXPRESSION ; CANCER ALPHA(V)-INTEGRIN EXPRESSION ; BREAST-CANCER ; BIODISTRIBUTION CHARACTERISTICS ; INITIAL EVALUATION ; F-18-LABELED RGD ; DRUG DEVELOPMENT ; IN-VITRO
英文摘要:

This report presents the synthesis of a cyclic RGD dimer conjugate, MAG(2)-G(3)-E[G(3)-c(RGDfK)](2) (MAG(2)-3G(3)-dimer, G(3) = Gly-Gly-Gly, MAG(2) = S-benzoyl mercaptoacetylglycylglycyl), and evaluation of its Tc-99m complex, (TcO)-Tc-99m(MAG(2)-3G(3)-dimer), as a new radiotracer for imaging the tumor integrin alpha(v)beta(3) expression.

An in vitro displacement assay was used to determine the integrin alpha(v)beta(3) binding affinity of MAG(2)-3G(3)-dimer against I-125-c(RGDyK) bound to U87MG human glioma cells. The athymic nude mice bearing U87MG glioma xenografts were used for biodistribution and planar imaging studies.

We found that (1) MAG(2) is such a highly effective bifunctional chelator that (TcO)-Tc-99m(MAG(2)-3G(3)-dimer) can be prepared in high yield (radiochemical purity > 95%) and with high specific activity (similar to 5 Ci/mu mol) using a kit formulation; (2) (TcO)-Tc-99m(MAG(2)-3G(3)-dimer) has very high solution stability in the kit matrix; and (3) (TcO)-Tc-99m(MAG(2)-3G(3)-dimer) has very fast clearance kinetics from the intestine, liver, and kidneys. Among the Tc-99m-labeled cyclic RGD peptides evaluated in the xenografted U87MG glioma models, (TcO)-Tc-99m(MAG(2)-3G(3)-dimer) has the best pharmacokinetics and tumor to background ratios (tumor/liver = 4.29 +/- 1.00 at 30 min postinjection and 8.29 +/- 1.50 at 120 min postinjection; tumor/kidney = 1.16 +/- 0.19 at 30 min postinjection and 2.49 +/- 0.25 at 120 min postinjection). Planar imaging studies showed that tumors in the glioma-bearing mice administered with (TcO)-Tc-99m(MAG(2)-3G(3)-dimer) can be visualized with excellent contrast as early as 15 min postinjection. (TcO)-Tc-99m(MAG(2)-3G(3)-dimer) was able to maintain its chemical integrity in kidneys (> 80% intact) and liver (> 95% intact) over the 2-h period. However, there was significant metabolism (> 50% of the injected radioactivity) detected in both urine and feces samples.

(TcO)-Tc-99m(MAG(2)-3G(3)-dimer) is a very attractive radiotracer for early detection of integrin alpha(v)beta(3)-positive tumors and has significant advantages over the F-18-labeled RGD peptide radiotracers with respect to the cost, availability, and easiness for routine clinical preparation.

语种: 英语
所属项目编号: R01 CA115883 A2 ; HL083961-01 ; DE-FG02-08ER64684
项目资助者: Purdue University and research ; National Cancer Institute (NCI) ; National Heart, Lung, and Blood Institute (NHLBI) ; Department of Energy
WOS记录号: WOS:000270980400018
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64206
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 100083, Peoples R China

Recommended Citation:
Shi, Jiyun,Wang, Lijun,Kim, Young-Seung,et al. (TcO)-Tc-99m(MAG(2)-3G(3)-dimer): a new integrin alpha(v)beta(3)-targeted SPECT radiotracer with high tumor uptake and favorable pharmacokinetics[J]. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,2009,36(11):1874-1884.
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