Investigating plasma volume expanders as novel macromolecular MRI-CEST contrast agents for tumor contrast-enhanced imaging

被引:8
|
作者
Consolino, Lorena [1 ,4 ]
Irrera, Pietro [1 ,2 ]
Romdhane, Feriel [1 ]
Anemone, Annasofia [1 ]
Longo, Dario Livio [3 ]
机构
[1] Univ Turin, Mol Imaging Ctr, Dept Mol Biotechnol & Hlth Sci, Turin, Italy
[2] Univ Campania Luigi Vanvitelli, Caserta, Italy
[3] Natl Res Council Italy CNR, Inst Biostruct & Bioimaging IBB, Via Nizza 52, I-10126 Turin, Italy
[4] Rhein Westfal TH Aachen, Inst Expt Mol Imaging, Dept Nanomed & Theranost, Aachen, Germany
基金
欧盟地平线“2020”;
关键词
chemical exchange saturation transfer; gadolinium; macromolecular agent; magnetic resonance imaging; plasma volume expander; SATURATION-TRANSFER MRI; IN-VIVO; DCE-MRI; VASCULAR-PERMEABILITY; DENTATE NUCLEUS; BLOOD-POOL; EXCHANGE; ALBUMIN; BINDING; DELIVERY;
D O I
10.1002/mrm.28778
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
Purpose: The aim of this study was to investigate two clinically approved plasma volume expanders (dextran 70 and voluven) as macromolecular MRI-chemical exchange saturation transfer (CEST) contrast agents to assess tumor vascular properties. Methods: CEST contrast efficiency of both molecules (6% w/v) was measured in vitro at various irradiation saturation powers (1-6 mu T for 5 s) and pH values (range, 5.5-7.9) and the exchange rate of hydroxyl protons was calculated. In vivo studies in a murine adenocarcinoma model (n = 4 mice for each contrast agent) upon i.v. injection provided CEST-derived perfusion tumor properties that were compared with those obtained with a gadolinium-based blood-pool agent (Gd-AAZTA-Madec). Results: In vitro measurements showed a marked CEST contrast dependency to pH, with higher CEST contrast at lower pH values for both molecules. The measured prototropic exchange rates confirmed a base-catalyzed exchange rate that was faster for dextran 70 in comparison to voluven. Both molecules showed a similar CEST contrast increase (Delta ST% > 3%) in the tumor tissue up to 30 min postinjection, with heterogeneous accumulation. In tumors receiving both CEST and T1-weighted agents, a voxel-by-voxel analysis indicated moderate spatial correlation of perfusion properties between voluven/dextran 70 and Gd-AAZTA-Madec, suggesting different distribution patterns according to their molecular size. Conclusions: The obtained results showed that both voluven and dextran 70 can be exploited as MRI-CEST contrast agents for evaluating tumor enhancement properties. Their increased accumulation in tumors and prolonged contrast enhancement promote their use as blood-pool MRI-CEST agents to examine tumor vascularization.
引用
收藏
页码:995 / 1007
页数:13
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