scholarly journals GdDO3NI allows imaging of hypoxia after brain injury

2021 ◽  
Author(s):  
Babak Moghadas ◽  
Vimala N Bharadwaj ◽  
John P Tobey ◽  
Yanqing Tian ◽  
Sarah E Stabenfeldt ◽  
...  

Purpose: In this study, we use the hypoxia targeting agent (GdDO3NI, a nitroimidazole-based T1 MRI contrast agent) for imaging hypoxia in the injured brain after experimental traumatic brain injury (TBI) using magnetic resonance imaging (MRI), and validate the results with immunohistochemistry (IHC) using pimonidazole. Methods: TBI induced mice (controlled cortical impact model) were imaged at 7T using a T2 weighted fast spin-echo sequence to estimate the extent of the injury. The mice were then were intravenously injected with either conventional T1 agent (gadoteridol) or GdDO3NI at 0.3 mmol/kg dose (n=5 for each cohort) along with pimonidazole (60 mg/kg). Mice were imaged pre- and post-contrast using a T1-weighted spin-echo sequence for three hours. Regions of interests were drawn on the brain injury region, the contralateral brain as well as on the cheek muscle region for comparison of contrast kinetics. Brains were harvested immediately post imaging for immunohistochemical analysis. Results: GdDO3NI is retained in the injury region for up to 3 hours post-injection (p< 0.05 compared to gadoteridol) while it rapidly clears out of the muscle region. On the other hand, conventional MRI contrast agent gadoteridol clears out of both the injury region and muscle rapidly, although with a relatively more delayed wash out in the injury region. Minimal contrast enhancement was seen for both agents in the contralateral hemisphere. Pimonidazole staining confirms the presence of hypoxia in both gadoteridol and GdDO3NI cohorts, and the later cohort shows good agreement with MRI contrast enhancement. Conclusion: GdDO3NI was successfully shown to visualize hypoxia in the brain post-TBI using T1-wt MRI.

2007 ◽  
Vol 232 (8) ◽  
pp. 1081-1089 ◽  
Author(s):  
Rongzuo Xu ◽  
Yanli Wang ◽  
Xuli Wang ◽  
Eun-Kee Jeong ◽  
Dennis L. Parker ◽  
...  

Macromolecular Gd(III) chelates are superior magnetic resonance imaging (MRI) contrast agents for blood pool and tumor imaging. However, their clinical development is limited by the safety concerns related to the slow excretion and long-term gadolinium tissue accumulation. A generation 6 PAMAM Gd(III) chelate conjugate with a cleavable disulfide spacer, PAMAM-G6-cystamine-(Gd-DO3A), was prepared as a biodegradable macromolecular MRI contrast agent with rapid excretion from the body. T1 and T2 relaxivities of the contrast agent were 11.6 and 13.3 m M−1sec−1 at 3T, respectively. Blood pool and tumor contrast enhancement of the agent were evaluated in female nude mice bearing MDA-MB-231 human breast carcinoma xenografts with a nondegradable conjugate PAMAM-G6-(Gd-DO3A) as a control. PAMAM-G6-cystamine-(Gd-DO3A) resulted in significant contrast enhancement in the blood for about 5 mins, and Gd-DO3A was released from the conjugate and rapidly excreted via renal filtration after the disulfide spacer was cleaved. The nondegradable control had much longer blood circulation and excreted more slowly from the body. PAMAM-G6-cystamine-(Gd-DO3A) also resulted in more prominent tumor contrast enhancement than the control. However, PAMAM-G6-cystamine-(Gd-DO3A) demonstrated high toxicity due to the intrinsic toxicity of PAMAM dendrimers. In conclusion, although PAMAM-G6-cystamine-(Gd-DO3A) showed some advantages compared with the nondegradable control, PAMAM dendrimers are not suitable carriers for biodegradable macromolecular MRI contrast agents, due to their high toxicity.


1993 ◽  
Vol 16 (3) ◽  
pp. 171-175 ◽  
Author(s):  
K.G. Go ◽  
J.W.M. Bulte ◽  
L. de Ley ◽  
T.H. The ◽  
R.L. Kamman ◽  
...  

RSC Advances ◽  
2019 ◽  
Vol 9 (25) ◽  
pp. 14051-14059
Author(s):  
Abdulrahman Ahmed Mahmood ◽  
Jianqi Zhang ◽  
Rufang Liao ◽  
Xiwei Pan ◽  
Dan Xu ◽  
...  

The acid-responsive pHLIP modified SPION as an MRI contrast agent for liver cancer diagnosis requires the validation of both the tumor-specific enhancement and a safe profile in cirrhosis.


Author(s):  
N. Riyahi-Alam ◽  
J. Behrouzkia ◽  
S. Haghgoo ◽  
A Seifalian ◽  
R Zohdi Aghdam. ◽  
...  

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1235
Author(s):  
Xiaohui Nan ◽  
Wenjia Lai ◽  
Dan Li ◽  
Jiesheng Tian ◽  
Zhiyuan Hu ◽  
...  

Derived from magnetotactic bacteria (MTB), magnetosomes consist of magnetite crystals enclosed within a lipid bilayer membrane and are known to possess advantages over artificially synthesized nanoparticles because of the narrow size distribution, uniform morphology, high purity and crystallinity, single magnetic domain, good biocompatibility, and easy surface modification. These unique properties have increasingly attracted researchers to apply bacterial magnetosomes (BMs) in the fields of biology and medicine as MRI imaging contrast agents. Due to the concern of biosafety, a long-term follow-up of the distribution and clearance of BMs after entering the body is necessary. In this study, we tracked changes of BMs in major organs of mice up to 135 days after intravenous injection using a combination of several techniques. We not only confirmed the liver as the well-known targeted organs of BMs, but also found that BMs accumulated in the spleen. Besides, two major elimination paths, as well as the approximate length of time for BMs to be cleared from the mice, were revealed. Together, the results not only confirm that BMs have high biocompatibility, but also provide a long-term in-vivo assessment which may further help to forward the clinical applications of BMs as an MRI contrast agent.


Author(s):  
Juliette Moreau ◽  
Maité Callewaert ◽  
Volodymyr Malytskyi ◽  
Céline Henoumont ◽  
Sorina N. Voicu ◽  
...  

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