A robust MRI contrast agent for specific display of the interstitial stream

Xiaohan Zhou; Junwei Cheng; Fangfei He; Zhuo Ao; Peisen Zhang; Jing Wang; Qing Li; Weinan Tang; Yiyan Zhou; Yan Liang; Yi Hou; Wentao Liu; Dong Han

doi:10.1039/d3na00118k

A robust MRI contrast agent for specific display of the interstitial stream

Nanoscale Adv. 2023 Jun 12;5(15):3905-3913. doi: 10.1039/d3na00118k. eCollection 2023 Jul 25.

Authors

Xiaohan Zhou^{1

2}, Junwei Cheng³, Fangfei He^{1

3}, Zhuo Ao^{1

2}, Peisen Zhang³, Jing Wang⁴, Qing Li⁵, Weinan Tang^{1

6}, Yiyan Zhou⁷, Yan Liang^{1

2}, Yi Hou³, Wentao Liu^{1

2}, Dong Han^{1

2}

Affiliations

¹ CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology Beijing 100190 China liuwentao@nanoctr.cn dhan@nanoctr.cn.
² University of Chinese Academy of Sciences Beijing 100139 China.
³ College of Life Science and Technology, Beijing University of Chemical Technology Beijing 100029 China houyi@iccas.ac.cn.
⁴ Center for Medical Device Evaluation, NMPA Beijing 100081 China.
⁵ Department of Nutrition, Southwest Hospital, Third Military Medical University (Army Medical University) Chongqing 400038 China.
⁶ Beijing Wandong Medical Technology Co. Beijing 100015 China.
⁷ College of Biological Sciences, University of California at Davis Sacramento CA 95817 USA.

Abstract

Experimental and clinical studies have reported phenomena of long-range fluid flow in interstitial space. However, its behaviours and functions are yet to be addressed. The imaging of the interstitial stream in vivo can clarify its transportation route and allow further understanding of physiological mechanisms and clinical relevance. Here to illustrate the route of the interstitial stream leading to the kidney, we design and synthesize a magnetic resonance imaging (MRI) contrast agent PAA-g-(DTPA-gadolinium). This MRI agent has a high longitudinal relaxivity for higher MRI contrast and large size to avoid leakage across the interstitial space. Using dynamic contrast enhanced MRI, histochemical staining, and trace element analysis of gadolinium, we track the nano-scale PAA-g-(DTPA-gadolinium) transported in the interstitial stream. The agent can be applied for a wide range of imaging and analysis of tissues and organs, thereby enabling advances in the fields of physiology, pathology, and pharmacology.