Langereis Sander, de Lussanet Quido G, van Genderen Marcel H P, Meijer E W, Beets-Tan Regina G H, Griffioen Arjan W, van Engelshoven Jos M A, Backes Walter H
Laboratory of Macromolecular and Organic Chemistry, Eindhoven University of Technology, Eindhoven, The Netherlands.
NMR Biomed. 2006 Feb;19(1):133-41. doi: 10.1002/nbm.1015.
Different generations of Gd(III)DTPA-terminated poly(propylene imine) dendrimers {G1 [n = 4 Gd(III) ions per molecule], G3 (n = 16) and G5 (n = 64)} and reference Gd(III)DTPA complex [G0 (n = 1)] were characterized in terms of (i) longitudinal (r1) and transverse (r2) relaxivities in mouse blood plasma, (ii) concentration detection limits in vitro and (iii) in vivo contrast-enhanced MR imaging (CE-MRI) in mice at 1.5 T. 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 G0 ionic r1 = 8.1 mM(-1) s(-1) and ionic r2 = 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 G0 (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, G0 and G1 showed a rapid tumor wash-in and wash-out, whereas G3 and G5 displayed a more gradual and prolonged tumor wash-in. In conclusion, both G0 and dendritic contrast agents G1, G3 and G5 are well suited for non-tissue-specific MRI of sub-millimeter-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.
对不同代数的钆（III）二乙三胺五乙酸封端的聚（丙烯亚胺）树枝状大分子{G1 [每分子含4个钆（III）离子]、G3（含16个）和G5（含64个）}以及参比钆（III）二乙三胺五乙酸配合物[G0（含1个）]进行了如下表征：（i）小鼠血浆中的纵向（r1）和横向（r2）弛豫率；（ii）体外浓度检测限；（iii）在1.5 T磁场下对小鼠进行的体内对比增强磁共振成像（CE-MRI）。进行了系列动态CE-MRI以监测磁共振成像造影剂在心脏、动脉、肾系统、肝脏、脾脏、膀胱和肿瘤周边的分布。弛豫率随分子量呈非线性增加（G0的离子r1 = 8.1 mM⁻¹ s⁻¹，离子r2 = 8.6 mM⁻¹ s⁻¹，到G5分别为19.3和25.0）。G5（8.1×10⁻⁸ M）的最小可检测树枝状大分子浓度比G0（3.1×10⁻⁵ M）低两个多数量级。使用每种造影剂进行系列CE-MRI可清晰显示亚毫米级大小的血管。动态CE-MRI显示所有造影剂均能及时经肾清除，但树枝状造影剂的较高代数显示出更强且持续时间更长的血液信号增强。此外，G0和G1显示出快速的肿瘤内流入和流出，而G3和G5显示出更缓慢且持续时间更长的肿瘤内流入。总之，G0以及树枝状造影剂G1、G3和G5均非常适合用于亚毫米级大小血管的非组织特异性磁共振成像以及评估小鼠肿瘤微循环特征。较高代数的树枝状造影剂显示出更低的浓度检测限，这表明它们未来可用于分子成像。
