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.
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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.
Daldrup-Link, Heike E.
中科院分区:
医学4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.

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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
肿瘤血管生成中的尿激酶和巨噬细胞。
DOI: 10.1038/bjc.1995.419
发表时间: 1995-10
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