Colocalization of Gadolinium-Diethylene Triamine Pentaacetic Acid With High-Molecular-Weight Molecules After Intracerebral Convection-Enhanced Delivery in Humans

Abstract BACKGROUND: Convection-enhanced delivery (CED) permits site-specific therapeutic drug delivery within interstitial spaces at increased dosages through circumvention of the blood-brain barrier. CED is currently limited by suboptimal methodologies for monitoring the delivery of therapeutic agents that would permit technical optimization and enhanced therapeutic efficacy. OBJECTIVE: To determine whether a readily available small-molecule MRI contrast agent, gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA), could effectively track the distribution of larger therapeutic agents. METHODS: Gd-DTPA was coinfused with the larger molecular tracer, 124I-labeled human serum albumin (124I-HSA), during CED of an EGFRvIII-specific immunotoxin as part of treatment for a patient with glioblastoma. RESULTS: Infusion of both tracers was safe in this patient. Analysis of both Gd-DTPA and 124I-HSA during and after infusion revealed a high degree of anatomical and volumetric overlap. CONCLUSION: Gd-DTPA may be able to accurately demonstrate the anatomic and volumetric distribution of large molecules used for antitumor therapy with high resolution and in combination with fluid-attenuated inversion recovery (FLAIR) imaging, and provide additional information about leaks into cerebrospinal fluid spaces and resection cavities. Similar studies should be performed in additional patients to validate our findings and help refine the methodologies we used.

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Gadolinium-free Magnetic Resonance Imaging of the Liver using an Oatp1-targeted Manganese(III) Porphyrin

10.1101/2021.08.04.455144 ◽

2021 ◽

Author(s):

Nivin N Nystrom ◽

Hanlin Liu ◽

Francisco M Martinez ◽

Xiao-an Zhang ◽

Timothy J Scholl ◽

...

Keyword(s):

Contrast Agent ◽

Organic Anion ◽

Mri Contrast Agent ◽

Liver Imaging ◽

Resonance Imaging ◽

Mri Contrast ◽

Organic Anion Transporting Polypeptide ◽

Diethylene Triamine ◽

Diethylene Triamine Pentaacetic Acid

Controversy surrounding gadolinium-based contrast agents (GBCAs) have rendered their continued utility highly contentious, but the liver-specific GBCA Gd(III) ethoxybenzyl-diethylene triamine pentaacetic acid (Gd(III)-EOB-DTPA) remains in use because it provides unique diagnostic information that could not be obtained by any other means. To address the need for an alternative liver-specific MRI contrast agent, we synthesized Mn(III) 20-(4-ethoxyphenyl) porphyrin-5,10,15-tricarboxylate (Mn(III)TriCP-PhOEt), which exhibited significantly higher r1 relaxivity than Gd(III)-EOB-DTPA, and targeted organic anion-transporting polypeptide 1 (Oatp1) channels as a biomarker of hepatocyte viability. Mn(III)TriCP-PhoEt increased the r1 relaxation rate of cells expressing rodent Oatp1a1 and human Oatp1b3, relative to control cells not expressing these liver channels. In mice, Mn(III)TriCP-PhoEt resulted in significant and specific increases in liver signal intensity on T1-weighted images, and significant decreases in liver T1 time relative to precontrast measurements. Our findings suggest that Mn(III)TriCP-PhOEt operates as a specific and sensitive MR contrast agent for in vivo liver imaging.

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Luminophore and Magnetic Multicore Nanoassemblies for Dual-Mode MRI and Fluorescence Imaging

Nanomaterials ◽

10.3390/nano10010028 ◽

2019 ◽

Vol 10 (1) ◽

pp. 28 ◽

Cited By ~ 4

Author(s):

Lénaïc Lartigue ◽

Marina Coupeau ◽

Mélanie Lesault

Keyword(s):

Magnetic Interaction ◽

Fluorescent Imaging ◽

Mri Contrast Agent ◽

Dual Mode ◽

Mri Contrast ◽

Additional Information ◽

Clinical Procedures ◽

Magnetic Resonance Imaging Mri ◽

Biological Entities ◽

Nanometric Size

Nanoassemblies encompass a large variety of systems (organic, crystalline, amorphous and porous). The nanometric size enables these systems to interact with biological entities and cellular organelles of similar dimensions (proteins, cells, …). Over the past 20 years, the exploitation of their singular properties as contrast agents has led to the improvement of medical imaging. The use of nanoprobes also allows the combination of several active units within the same nanostructure, paving the way to multi-imaging. Thus, the nano-object provides various additional information which helps simplify the number of clinical procedures required. In this review, we are interested in the combination between fluorescent units and magnetic nanoparticles to perform dual-mode magnetic resonance imaging (MRI) and fluorescent imaging. The effect of magnetic interaction in multicore iron oxide nanoparticles on the MRI contrast agent properties is highlighted.

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Continuous intraputamenal convection-enhanced delivery in adult rhesus macaques

Journal of Neurosurgery ◽

10.3171/2015.1.jns132345 ◽

2015 ◽

Vol 123 (6) ◽

pp. 1569-1577 ◽

Cited By ~ 8

Author(s):

Xiaotong Fan ◽

Brian D. Nelson ◽

Yi Ai ◽

David K. Stiles ◽

Don M. Gash ◽

...

Keyword(s):

Rhesus Monkeys ◽

Rhesus Macaques ◽

Insertion Site ◽

Volume Of Distribution ◽

Mri Contrast Agent ◽

Convection Enhanced Delivery ◽

Mri Contrast ◽

Chronic Infusion ◽

System 1 ◽

The Brain

OBJECT Assessing the safety and feasibility of chronic delivery of compounds to the brain using convection-enhanced delivery (CED) is important for the further development of this important therapeutic technology. The objective of this study was to follow and model the distribution of a compound delivered by CED into the putamen of rhesus monkeys. METHODS The authors sequentially implanted catheters into 4 sites spanning the left and right putamen in each of 6 rhesus monkeys. The catheters were connected to implanted pumps, which were programmed to deliver a 5-mM solution of the MRI contrast agent Gd-DTPA at 0.1 μl/minute for 7 days and 0.3 μl/minute for an additional 7 days. The animals were followed for 28 days per implant cycle during which they were periodically examined with MRI. RESULTS All animals survived the 4 surgeries with no deficits in behavior. Compared with acute infusion, the volume of distribution (Vd) increased 2-fold with 7 days of chronic infusion. Increasing the flow rate 3-fold over the next week increased the Vd an additional 3-fold. Following withdrawal of the compound, the half-life of Gd-DTPA in the brain was estimated as 3.1 days based on first-order pharmacokinetics. Histological assessment of the brain showed minimal tissue damage limited to the insertion site. CONCLUSIONS These results demonstrate several important features in the development of a chronically implanted pump and catheter system: 1) the ability to place catheters accurately in a predetermined target; 2) the ability to deliver compounds in a chronic fashion to the putamen; and 3) the use of MRI and MR visible tracers to follow the evolution of the infusion volume over time.

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Application of aziridinium ring opening for preparation of optically active diamine and triamine analogues: highly efficient synthesis and evaluation of DTPA-based MRI contrast enhancement agents

RSC Advances ◽

10.1039/c5ra11306g ◽

2015 ◽

Vol 5 (115) ◽

pp. 94571-94581 ◽

Cited By ~ 5

Author(s):

Xiang Sun ◽

Yunwei Chen ◽

Ningjie Wu ◽

Chi Soo Kang ◽

Hyun A. Song ◽

...

Keyword(s):

Contrast Enhancement ◽

Ring Opening ◽

Optically Active ◽

Efficient Synthesis ◽

Mri Contrast ◽

Diethylene Triamine ◽

Highly Efficient ◽

Diethylene Triamine Pentaacetic Acid ◽

Nitrogen Nucleophiles ◽

Aziridinium Ions

Ring opening of aziridinium ions with nitrogen nucleophiles was applied to highly efficient synthesis of optically active vicinal diamines and diethylene triamine pentaacetic acid (DTPA) analogues.

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Simultaneous Recordings of Gadolinium-based MRI Contrast Agent and PET Tracer Arterial Input Function in Mice Using an Extracorporeal Shunt

10.1055/s-0039-1683687 ◽

2019 ◽

Author(s):

P Backhaus ◽

F Büther ◽

L Wachsmuth ◽

L Frohwein ◽

KP Schäfers ◽

...

Keyword(s):

Contrast Agent ◽

Arterial Input Function ◽

Input Function ◽

Mri Contrast Agent ◽

Mri Contrast ◽

Pet Tracer

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Evaluation of non-targeting, C- or N-pH (low) insertion peptide modified superparamagnetic iron oxide nanoclusters for selective MRI of liver tumors and their potential toxicity in cirrhosis

RSC Advances ◽

10.1039/c9ra02430a ◽

2019 ◽

Vol 9 (25) ◽

pp. 14051-14059

Author(s):

Abdulrahman Ahmed Mahmood ◽

Jianqi Zhang ◽

Rufang Liao ◽

Xiwei Pan ◽

Dan Xu ◽

...

Keyword(s):

Iron Oxide ◽

Liver Cancer ◽

Contrast Agent ◽

Cancer Diagnosis ◽

Liver Tumors ◽

Superparamagnetic Iron Oxide ◽

Mri Contrast Agent ◽

Potential Toxicity ◽

Mri Contrast ◽

Specific Enhancement

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.

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Synthesis and characterization of targeted superparamagnetic MRI contrast agent MnFe2O4-chitosan-folate

IOP Conference Series Materials Science and Engineering ◽

10.1088/1757-899x/1053/1/012019 ◽

2021 ◽

Vol 1053 (1) ◽

pp. 012019

Author(s):

A.H. Gunawan ◽

Y. Sugiharto ◽

S. Yulianto ◽

A. Fikri

Keyword(s):

Contrast Agent ◽

Mri Contrast Agent ◽

Synthesis And Characterization ◽

Mri Contrast

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Gd2O3 nanoparticles as a positive MRI contrast agent for cell uptake

2010 17th Iranian Conference of Biomedical Engineering (ICBME) ◽

10.1109/icbme.2010.5705030 ◽

2010 ◽

Author(s):

N. Riyahi-Alam ◽

J. Behrouzkia ◽

S. Haghgoo ◽

A Seifalian ◽

R Zohdi Aghdam. ◽

...

Keyword(s):

Contrast Agent ◽

Mri Contrast Agent ◽

Cell Uptake ◽

Mri Contrast ◽

Gd2o3 Nanoparticles

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Biocompatibility of Bacterial Magnetosomes as MRI Contrast Agent: A Long-Term In Vivo Follow-Up Study

Nanomaterials ◽

10.3390/nano11051235 ◽

2021 ◽

Vol 11 (5) ◽

pp. 1235

Author(s):

Xiaohui Nan ◽

Wenjia Lai ◽

Dan Li ◽

Jiesheng Tian ◽

Zhiyuan Hu ◽

...

Keyword(s):

Contrast Agent ◽

Magnetic Domain ◽

Bilayer Membrane ◽

The Body ◽

Mri Contrast Agent ◽

Mri Imaging ◽

Mri Contrast

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.

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