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Dynamic contrast-enhanced CEST MRI using a low molecular weight dextran

Han, Zheng ; Chen, Chuheng ; Xu, Xiang ; Bai, Renyuan ; Staedtke, Verena ; Huang, Jianpan ; Chan, Kannie W Y ; Xu, Jiadi ; Kamson, David O and Wen, Zhibo , et al. (2022) In NMR in Biomedicine 35(3).
Abstract

Natural and synthetic sugars have great potential for developing highly biocompatible and translatable chemical exchange saturation transfer (CEST) MRI contrast agents. In this study, we aimed to develop the smallest clinically available form of dextran, Dex1 (molecular weight, MW ~ 1 kDa), as a new CEST agent. We first characterized the CEST properties of Dex1 in vitro at 11.7 T and showed that the Dex1 had a detectable CEST signal at ~1.2 ppm, attributed to hydroxyl protons. In vivo CEST MRI studies were then carried out on C57BL6 mice bearing orthotopic GL261 brain tumors (n = 5) using a Bruker BioSpec 11.7 T MRI scanner. Both steady-state full Z-spectral images and single offset (1.2 ppm) dynamic dextran-enhanced (DDE) images were... (More)

Natural and synthetic sugars have great potential for developing highly biocompatible and translatable chemical exchange saturation transfer (CEST) MRI contrast agents. In this study, we aimed to develop the smallest clinically available form of dextran, Dex1 (molecular weight, MW ~ 1 kDa), as a new CEST agent. We first characterized the CEST properties of Dex1 in vitro at 11.7 T and showed that the Dex1 had a detectable CEST signal at ~1.2 ppm, attributed to hydroxyl protons. In vivo CEST MRI studies were then carried out on C57BL6 mice bearing orthotopic GL261 brain tumors (n = 5) using a Bruker BioSpec 11.7 T MRI scanner. Both steady-state full Z-spectral images and single offset (1.2 ppm) dynamic dextran-enhanced (DDE) images were acquired before and after the intravenous injection of Dex1 (2 g/kg). The steady-state Z-spectral analysis showed a significantly higher CEST contrast enhancement in the tumor than in contralateral brain (∆MTRasym 1.2 ppm = 0.010 ± 0.006 versus 0.002 ± 0.008, P = 0.0069) at 20 min after the injection of Dex1. Pharmacokinetic analyses of DDE were performed using the area under the curve (AUC) in the first 10 min after Dex1 injection, revealing a significantly higher uptake of Dex1 in the tumor than in brain tissue for tumor-bearing mice (AUC[0-10 min] = 21.9 ± 4.2 versus 5.3 ± 6.4%·min, P = 0.0294). In contrast, no Dex1 uptake was foundling in the brains of non-tumor-bearing mice (AUC[0-10 min] = -1.59 ± 2.43%·min). Importantly, the CEST MRI findings were consistent with the measurements obtained using DCE MRI and fluorescence microscopy, demonstrating the potential of Dex1 as a highly translatable CEST MRI contrast agent for assessing tumor hemodynamics.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
NMR in Biomedicine
volume
35
issue
3
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85119377042
  • pmid:34779550
ISSN
0952-3480
DOI
10.1002/nbm.4649
project
Natural sugar as an MRI contrast agent for cancer diagnosis
language
English
LU publication?
yes
id
f307d5df-0b92-4598-b0e6-0382e4b1605a
date added to LUP
2021-11-16 14:04:27
date last changed
2024-04-20 15:24:38
@article{f307d5df-0b92-4598-b0e6-0382e4b1605a,
  abstract     = {{<p>Natural and synthetic sugars have great potential for developing highly biocompatible and translatable chemical exchange saturation transfer (CEST) MRI contrast agents. In this study, we aimed to develop the smallest clinically available form of dextran, Dex1 (molecular weight, MW ~ 1 kDa), as a new CEST agent. We first characterized the CEST properties of Dex1 in vitro at 11.7 T and showed that the Dex1 had a detectable CEST signal at ~1.2 ppm, attributed to hydroxyl protons. In vivo CEST MRI studies were then carried out on C57BL6 mice bearing orthotopic GL261 brain tumors (n = 5) using a Bruker BioSpec 11.7 T MRI scanner. Both steady-state full Z-spectral images and single offset (1.2 ppm) dynamic dextran-enhanced (DDE) images were acquired before and after the intravenous injection of Dex1 (2 g/kg). The steady-state Z-spectral analysis showed a significantly higher CEST contrast enhancement in the tumor than in contralateral brain (∆MTRasym 1.2 ppm = 0.010 ± 0.006 versus 0.002 ± 0.008, P = 0.0069) at 20 min after the injection of Dex1. Pharmacokinetic analyses of DDE were performed using the area under the curve (AUC) in the first 10 min after Dex1 injection, revealing a significantly higher uptake of Dex1 in the tumor than in brain tissue for tumor-bearing mice (AUC[0-10 min] = 21.9 ± 4.2 versus 5.3 ± 6.4%·min, P = 0.0294). In contrast, no Dex1 uptake was foundling in the brains of non-tumor-bearing mice (AUC[0-10 min] = -1.59 ± 2.43%·min). Importantly, the CEST MRI findings were consistent with the measurements obtained using DCE MRI and fluorescence microscopy, demonstrating the potential of Dex1 as a highly translatable CEST MRI contrast agent for assessing tumor hemodynamics.</p>}},
  author       = {{Han, Zheng and Chen, Chuheng and Xu, Xiang and Bai, Renyuan and Staedtke, Verena and Huang, Jianpan and Chan, Kannie W Y and Xu, Jiadi and Kamson, David O and Wen, Zhibo and Knutsson, Linda and van Zijl, Peter C M and Liu, Guanshu}},
  issn         = {{0952-3480}},
  language     = {{eng}},
  number       = {{3}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{NMR in Biomedicine}},
  title        = {{Dynamic contrast-enhanced CEST MRI using a low molecular weight dextran}},
  url          = {{http://dx.doi.org/10.1002/nbm.4649}},
  doi          = {{10.1002/nbm.4649}},
  volume       = {{35}},
  year         = {{2022}},
}