Evaluation of the novel USPIO GEH121333 for MR imaging of cancer immune responses.
Evaluation of the novel USPIO GEH121333 for MR imaging of cancer immune responses.
复制标题
对癌症免疫反应MR成像的新型USPIO GEH121333的评估。
DOI:
10.1002/cmmi.1526
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发表时间:
2013-05
影响因子:
--
通讯作者:
Daldrup-Link, Heike E.
中科院分区:
文献类型:
--
作者:
Shi, Qiaoyun;Pisani, Laura J.;Lee, Yauk K.;Messing, Solomon;Ansari, Celina;Bhaumik, Srabani;Lowery, Lisa;Lee, Brian D.;Meyer, Dan E.;Daldrup-Link, Heike E.
Tumor-associated macrophages (TAM) maintain a chronic inflammation in cancers, which is associated with tumor aggressiveness and poor prognosis. The purpose of this study was to: (1) evaluate the pharmacokinetics and tolerability of the novel ultrasmall superparamagnetic iron oxide nanoparticle (USPIO) compound GEH121333; (2) assess whether GEH121333 can serve as a MR imaging biomarker for TAM; and (3) compare tumor MR enhancement profiles between GEH121333 and ferumoxytol. Blood half-lives of GEH121333 and ferumoxytol were measured by relaxometry (n = 4 each). Tolerance was assessed in healthy rats injected with high dose GEH121333, vehicle or saline (n = 4 each). Animals were monitored for 7 days regarding body weight, complete blood counts and serum chemistry, followed by histological evaluation of visceral organs. MR imaging was performed on mice harboring MMTV-PyMT-derived breast adenocarcinomas using a 7 T scanner before and up to 72 h post-injection (p.i.) of GEH121333 (n = 10) or ferumoxytol (n = 9). Tumor R1, R2* relaxation rates were compared between different experimental groups and time points, using a linear mixed effects model with a random effect for each animal. MR data were correlated with histopathology. GEH121333 showed a longer circulation half-life than ferumoxytol. Intravenous GEH121333 did not produce significant adverse effects in rats. All tumors demonstrated significant enhancement on T1, T2 and T2*-weighted images at 1, 24, 48 and 72 h p.i. GEH121333 generated stronger tumor T2* enhancement than ferumoxytol. Histological analysis verified intracellular compartmentalization of GEH121333 by TAM at 24, 48 and 72 h p.i. MR imaging with GEH121333 nanoparticles represents a novel biomarker for TAM assessment. This new USPIO MR contrast agent provides a longer blood half-life and better TAM enhancement compared with the iron supplement ferumoxytol. Copyright © 2013 John Wiley & Sons, Ltd. Supporting information may be found in the online version of this paper
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影响因子:
8.8
作者:
Hildenbrand, R.;Dilger, I.;Hoerlin, A.;Stutte, H. J.
通讯作者:
Stutte, H. J.
DOI:
10.1158/1078-0432.ccr-10-3420
发表时间:
2011-09-01
期刊:
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子:
--
作者:
Daldrup-Link HE;Golovko D;Ruffell B;Denardo DG;Castaneda R;Ansari C;Rao J;Tikhomirov GA;Wendland MF;Corot C;Coussens LM
通讯作者:
Coussens LM
影响因子:
4.8
作者:
Mizutani, Kosuke;Sud, Sudha;Pienta, Kenneth J.
通讯作者:
Pienta, Kenneth J.
影响因子:
2.2
作者:
Kawamura, Kyoko;Komohara, Yoshihiro;Takeya, Motohiro
通讯作者:
Takeya, Motohiro
影响因子:
5.3
作者:
GUY, CT;CARDIFF, RD;MULLER, WJ
通讯作者:
MULLER, WJ