Magnetic resonance imaging enhancement of normal tissues and tumors using macromolecular Gd-based cascade polymer contrast agents - Preclinical evaluations
Magnetic resonance imaging enhancement of normal tissues and tumors using macromolecular Gd-based cascade polymer contrast agents - Preclinical evaluations
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DOI：
10.1097/01.rli.0000246145.25993.d1
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发表时间：
2006-12-01
影响因子：
6.7
通讯作者：
Brasch, Robert C.
中科院分区：
文献类型：
--
作者：
Raatschen, Hans-Juergen;Fu, Yanjun;Brasch, Robert C.
Objectives: We sought to compare magnetic resonance imaging (MRI) enhancement using 4 novel macromolecular polyethyleneglycol (PEG)-based cascade-polymer gadolinium contrast agents (macromolecular contrast media) in normal soft tissues and a breast cancer model.Materials and Methods: Four candidate PEG cascade polymers with effective molecular weights of 74, 82, 106, and 132 kDa, respectively, and T1-relaxivities of 8.1, 9.1, 9.7, and 10.0, respectively (at 2 Tesla and 37 degrees C in HEPES buffer), initially were used to characterize liver and kidney MRI-enhancement patterns in normal Sprague-Dawley rats (n = 4-5 per contrast agent). Kinetic analysis of dynamic MRI enhancement was used in 8 nude rats bearing MDA-MB 435 breast cancers to estimate fractional plasma volume and apparent endothelial leakiness (K-PS) in tumors and muscle.Results: Soft-tissue enhancement patterns followed closely the blood enhancement over the course of 30-50 minutes with estimated blood half-lives between 23 and 73 minutes, which varied with effective molecular weights. The 2 smaller compounds yielded measurable leaks in normal muscle [K-PS = 204 and 56 mu L/ (min (.) 100 cm(3)), respectively], whereas the 2 larger molecules did not leak in muscle [K-PS = 0 mu L/(min (.) 100 cm(3))]; however, MRI-assayed leakiness of tumor vessels with respect to those 2 larger macromolecular contrast media was 68 +/- 27 and 16 +/- 8 mu L/(min (.) 100 cm(3)), respectively.Conclusions: Two relatively large (effective molecular weight > 82 kDa) PEG-based cascade polymer contrast agents were well-suited for MRI quantification of tissue plasma volume and for differentiating leaky cancer microvessels from nonleaky normal vessels.
