Evaluation of Gd(III)DTPA-terminated poly(propylene imine) dendrimers as contrast agents for MR imaging

Evaluation of Gd(III)DTPA-terminated poly(propylene imine) dendrimers as contrast agents for MR imaging
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DOI:
10.1002/nbm.1015
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发表时间:
2006-02-01
期刊:
影响因子:
2.9
通讯作者:
Backes, WH
Backes, WH
中科院分区:
医学3区
文献类型:
--
作者:
Langereis, S;de Lussanet, QG;Backes, WH

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不同代Gd(III)DTPA封端的聚(丙烯亚胺)枝晶{G1 [n = 4 Gd(III)离子/分子]、G3(n = 16)和G5(n = 64)}和参考Gd(III)DTPA络合物[GO(it = 1)]的特征在于(i)小鼠血浆中的纵向(r(1))和横向(r(2))弛豫率,(ii)体外浓度检测限和(iii)在1.5T下小鼠体内对比增强MR成像(CE-MRI)。采用连续和动态CE-MRI监测造影剂在心脏、动脉、肾脏、肝脏、脾脏、膀胱和肿瘤周围的分布。弛豫率随分子量非线性地增加(对于GO离子r(1)= 8.1 mM(-1)s(-1)和离子r(2)= 8.6 mM(-1)s(-1),G5分别为19.3和25.0)。G5的最小可检测树枝状聚合物浓度(8.1 × 10(-8)M)比GO的最小可检测树枝状聚合物浓度(3.1 × 10(-5)M)低两个数量级以上。使用每种造影剂的连续CE-MRI可很好地显示亚毫米大小的血管。动态CE-MRI显示所有造影剂的及时肾脏清除,但更高代的树突状造影剂的血液信号增强更强和更长。此外,GO和G1显示出快速的肿瘤洗入和洗出,而G3和G5显示出更渐进和更长的肿瘤洗出。总之,GO和树突状造影剂G1. G3和G5非常适合于亚毫米级血管的非组织特异性MRI和评价小鼠肿瘤微循环特性。更高代的树突状造影剂显示出较低的浓度检测限,这表明它们未来可用于分子成像版权所有(c)2006 John Wiley & Sons,Ltd.
Different generations of Gd(III)DTPA-terminated poly(propylene imine) dendrituers {G1 [n = 4 Gd(III) ions per molecule], G3 (n = 16) and G5 (n = 64)} and reference Gd(III)DTPA complex [GO (it = 1)] were characterized in terms of (i) longitudinal (r(1)) and transverse (r(2)) relaxivities in mouse blood plasma, (ii) concentration detection limits ill vitro and (iii) in vivo contrast-enhanced MR imaging (CE-MRI) in mice at 1.5T. Serial and dynamic CE-MRI were performed to monitor the distribution of MRI contrast agent in the heart, arteries, renal system, liver, spleen, bladder and tumor periphery. The relaxivities increased non-linearly with molecular weight (for GO ionic r(1) = 8.1 mM(-1) s(-1) and ionic r(2) = 8.6 mM(-1) s(-1) to G5 19.3 and 25.0, respectively). The minimal detectable dendrimer concentration was more than two orders of magnitude lower for G5 (8.1 x 10(-8) m) than for GO (3.1 x 10(-5) M). Sub-millimeter-sized blood vessels were well visualized with serial CE-MRI with each contrast agent. Dynamic CE-MRI showed timely renal clearance for all contrast agents, but a stronger and a prolonged blood signal enhancement for the higher generations of the dendritic contrast agent. Moreover, GO and G1 showed a rapid tumor wash-in and wash-out, whereas G3 and G5 displayed a more gradual and prolonged tumor wash-ill. In conclusion, both GO and dendritic contrast agents G1. G3 and G5 are well suited for non-tissue-specific MRI Of submillimeter-sized blood vessels and evaluating tumor microcirculatory characteristics in mice. Higher generations of dendritic contrast agents display lower concentration detection limits, which Suggests their future use for molecular imaging Copyright (c) 2006 John Wiley & Sons, Ltd.