Evaluation of a novel macromolecular cascade-polymer contrast medium for dynamic contrast-enhanced MRI monitoring of antiangiogenic bevacizumab therapy in a human melanoma model.
Evaluation of a novel macromolecular cascade-polymer contrast medium for dynamic contrast-enhanced MRI monitoring of antiangiogenic bevacizumab therapy in a human melanoma model.
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DOI：
10.1016/j.acra.2013.07.010
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发表时间：
2013-10
影响因子：
4.8
通讯作者：
Brasch, Robert C.
中科院分区：
文献类型：
--
作者：
Cyran, Clemens C.;Fu, Yanjun;Rogut, Victor;Chaopathomkul, Bundit;Wendland, Michael F.;Shames, David M.;Brasch, Robert C.
关键词：
To assess the applicability of a novel macromolecular polyethylene glycol (PEG)-core gadolinium contrast agent for monitoring early antiangiogenic effects of bevacizumab using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). Athymic rats (n = 26) implanted with subcutaneous human melanoma xenografts underwent DCE-MRI at 2.0 T using two different macromolecular contrast agents. The PEG core cascade polymer PEG12,000-Gen4-(Gd-DOTA)16, designed for clinical development, was compared to the prototype, animal-only, macromolecular contrast medium (MMCM) albumin-(Gd-DTPA)35. The treatment (n = 13) and control (n = 13) group was imaged at baseline and 24 hours after a single dose of bevacizumab (1 mg) or saline to quantitatively assess the endothelial-surface permeability constant (KPS, μL·min·100 cm3) and the fractional plasma volume (fPV,%), using a two-compartment kinetic model. Mean KPS values, assessed with PEG12,000-Gen4-(Gd-DOTA)16, declined significantly (P< .05) from 29.5 ± 10 μL·min·100cm3 to 10.4±7.8 μL·min·100 cm3 by 24 hours after a single dose of bevacizumab. In parallel, KPS values quantified using the prototype MMCM albumin-(Gd-DTPA)35 showed an analogous, significant decline (P < .05) in the therapy group. No significant effects were detected on tumor vascularity or on microcirculatory parameters in the control group between the baseline and the follow-up scan at 24 hours. DCE-MRI enhanced with the novel MMCM PEG12,000-Gen4-(Gd-DOTA)16 was able to monitor the effects of bevacizumab on melanoma xenografts within 24 hours of a single application, validated by the prototype, animal-only albumin-(Gd-DTPA)35. PEG12,000-Gen4-(Gd-DOTA)16 may be a promising candidate for further clinical development as a macromolecular blood pool contrast MRI agent.
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DOI：
10.1084/jem.174.5.1275
发表时间：
1991-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dvorak HF;Sioussat TM;Brown LF;Berse B;Nagy JA;Sotrel A;Manseau EJ;Van de Water L;Senger DR
通讯作者：
Senger DR
影响因子：
45.3
作者：
Ratain, Mark J.;Eisen, Tim;O'Dwyer, Peter J.
通讯作者：
O'Dwyer, Peter J.
影响因子：
6.7
作者：
Raatschen, Hans-Juergen;Fu, Yanjun;Brasch, Robert C.
通讯作者：
Brasch, Robert C.
影响因子：
5.9
作者：
Cyran, Clemens C.;Sennino, Barbara;Brasch, Robert C.
通讯作者：
Brasch, Robert C.
影响因子：
3.3
作者：
Cyran, Clemens C.;Sennino, Barbara;Fu, Yanjun;Rogut, Victor;Shames, David M.;Chaopathomkul, Bundit;Wendland, Michael F.;McDonald, Donald M.;Brasch, Robert C.;Raatschen, Hans-Juergen
通讯作者：
Raatschen, Hans-Juergen