Synthesis and characterization of gadolinium-Peptidomimetic complex as an αvβ3 integrin targeted MR contrast agent.
Synthesis and characterization of gadolinium-Peptidomimetic complex as an αvβ3 integrin targeted MR contrast agent.
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DOI：
10.1016/j.bmcl.2015.03.092
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发表时间：
2015
影响因子：
2.7
通讯作者：
Brechbiel, Martin W.
中科院分区：
文献类型：
--
作者：
Kim, Young-Seung;Zhou, Yang;Bryant, Henry, Jr.;Milenic, Diane E.;Baidoo, Kwamena E.;Lewis, Bobbi K.;Frank, Joseph A.;Brechbiel, Martin W.
There is growing interest in small and rigid peptidomimetic αvβ3 integrin antagonists that are readily synthesized and characterized and amenable to physiological conditions. Peptidomimetic 4-[2-(3,4,5,6-tetrahydropyrimidine-2-ylamino)ethyloxy]benzoyl-2-[N-(3-amino-neopenta-1-carbamyl)]-aminoethylsulfonyl-amino-β-alanine (IAC) was successfully conjugated to DOTA, complexed with Gd(III) and radiolabeled with 153Gd. Radioassay results demonstrated specificity of the labeled conjugate by blocking ~95% binding with the addition of a 50-fold molar excess of cold IAC to the reaction solution. Relaxometry was used to support the hypothesis that the specificity of the Gd-peptidomimetic targeting αvβ3 integrin would increase the contrast and therefore enhance the sensitivity of an MRI scan of αvβ3 integrin positive tissues. Magnetic resonance imaging of cell pellets (M21 human melanoma) was also performed, and the images clearly show that cells reacted with Gd(III)-DOTA-IAC display a brighter image than cells without the Gd(III)-DOTA-IAC contrast agent. In addition, Gd(III)-DOTA-IAC and IAC, with IC50 of 300 nM and 230 nM, respectively, are 2.1 and 2.7 times more potent than c(RGDfK) whose IC50 is 625 nM. This promising preliminary data fuels further investigation of DOTA-IAC conjugates for targeting tumor associated angiogenesis and αvβ3 integrin positive tumors using magnetic resonance imaging.
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影响因子：
2.8
作者：
Prantner, Andrew M;Sharma, Vijay;Piwnica-Worms, David
通讯作者：
Piwnica-Worms, David
影响因子：
16.6
作者：
通讯作者：
--
影响因子：
2.7
作者：
Kim, Young-Seung;Nwe, Kido;Milenic, Diane E.;Brechbiel, Martin W.;Satz, Stanley;Baidoo, Kwamena E.
通讯作者：
Baidoo, Kwamena E.
影响因子：
62.1
作者：
Villaraza, Aaron Joseph L.;Bumb, Ambika;Brechbiel, Martin W.
通讯作者：
Brechbiel, Martin W.
影响因子：
15.9
作者：
FELDINGHABERMANN, B;MUELLER, BM;CHERESH, DA
通讯作者：
CHERESH, DA