Gadofosveset‐based biomarker of tissue albumin concentration: Technical validation in vitro and feasibility in vivo

Richardson, Owen C; Bane, Octavia; Scott, Marietta; Tanner, Steven F.; Waterton, John C.; Sourbron, Steven; Carroll, Timothy J.; Buckley, David L.

doi:10.1002/mrm.25128

Cited by 14 publications

(14 citation statements)

References 59 publications

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“…Gadofosveset binds reversibly to serum albumin, increasing its molecular weight from 0.9 to 67 kDa. Under physiological conditions, albumin has a low transcapillary exchange rate into the interstitial compartment, estimated to be on the order of 5% per hour, which explains the propensity of gadofosveset to remain within blood vessels ( Richardson et al, 2015 ). In both species, gadofosveset did not reveal dural lymphatics, especially on T1-black blood images ( Figure 2 and Figure 2—figure supplement 1 ).…”

Section: Resultsmentioning

confidence: 99%

Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI

Absinta

Nair

et al. 2017

eLife

453

485

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Here, we report the existence of meningeal lymphatic vessels in human and nonhuman primates (common marmoset monkeys) and the feasibility of noninvasively imaging and mapping them in vivo with high-resolution, clinical MRI. On T2-FLAIR and T1-weighted black-blood imaging, lymphatic vessels enhance with gadobutrol, a gadolinium-based contrast agent with high propensity to extravasate across a permeable capillary endothelial barrier, but not with gadofosveset, a blood-pool contrast agent. The topography of these vessels, running alongside dural venous sinuses, recapitulates the meningeal lymphatic system of rodents. In primates, meningeal lymphatics display a typical panel of lymphatic endothelial markers by immunohistochemistry. This discovery holds promise for better understanding the normal physiology of lymphatic drainage from the central nervous system and potential aberrations in neurological diseases.

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Section: Resultsmentioning

confidence: 99%

Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI

Absinta

Nair

et al. 2017

eLife

453

485

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“…Consequently, considering that elimination half-lives in humans are six to nine fold longer than in mice, these results indicated that the one order of magnitude higher affinity constant to HSA for Gd-AAZTA-MADEC may allow robust steady-state MRI angiographic acquisitions [40]. Beyond angiography, recent studies have utilized MS-325 as a biomarker for tissue albumin concentration for assessing reperfused myocardial infarction [41]. The design of a new blood pool agent with optimized albumin binding properties may allow further improvements of this new clinical indication.…”

Section: Discussionmentioning

confidence: 99%

Gd-AAZTA-MADEC, an improved blood pool agent for DCE-MRI studies on mice on 1 T scanners

et al. 2016

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A novel MRI blood-pool contrast agent (Gd-AAZTA-MADEC) has been compared with established blood pool agents for tumor contrast enhanced images and angiography. Synthesis, relaxometric properties, albumin binding affinity and pharmacokinetic profiles are reported. For in vivo studies, angiographic images and tumor contrast enhanced images were acquired on mice with benchtop 1T-MRI scanners and compared with MS-325, B22956/1 and B25716/1. The design of this contrast agent involved the elongation of the spacer between the targeting deoxycholic acid moiety and the Gd-AAZTA imaging reporting unit that drastically changed either the binding affinity to albumin (KA(HSA) = 8.3x10 5 M-1) and the hydration state of the Gd ion (q=2) in comparison to the recently reported B25716/1. The very markedly high binding affinity towards mouse and human serum albumins resulted in peculiar pharmacokinetics and relaxometric properties. The NMRD profiles clearly indicated that maximum efficiency is attainable at magnetic field strength of 1T. In vivo studies showed high enhancement of the vasculature and a prolonged accumulation inside tumor. The herein reported pre-clinical imaging studies show that a great benefit arises from the combination of a benchtop MRI scanner operating at 1T and the albuminbinding Gd-AAZTA-MADEC complex, for pursuing enhanced angiography and improved characterization of tumor vascular microenvironment.

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“…48 Prior to in vivo reported. 49,50 The analysis of the myocardial uptake curve with the 2CX model resulted in good agreement of MBF estimation, with some trends towards higher MBF values and lower variability for Vasovist. Similar observations were noted by Jerosch-Herold et al, 51 who suggested that the use of an intravascular (instead of an extracellular) contrast agent allows for a reduction of the degrees of freedom for modeling tissue uptake (with a compartment BTEX model) and hence results in improved accuracy of MBF estimation.…”

Section: Discussionmentioning

confidence: 79%

“…Because of its long circulation time, it was primarily designated for contrast‐enhanced angiography, but it has also been studied for cardiac applications, including perfusion estimation . Prior to in vivo application in the current study, the relaxivity of Vasovist was measured in a solution of saline and bovine serum albumin, yielding a relaxivity constant of ≈ 5mM −1 s −1 , which is significantly higher than that measured for Gadovist (≈ 4mM −1 s −1 ) and in line with values previously reported . The analysis of the myocardial uptake curve with the 2CX model resulted in good agreement of MBF estimation, with some trends towards higher MBF values and lower variability for Vasovist.…”

Section: Discussionmentioning

confidence: 99%

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Extended quantitative dynamic contrast‐enhanced cardiac perfusion imaging in mice using accelerated data acquisition and spatially distributed, two‐compartment exchange modeling

Kwiatkowski

Kozerke

2019

NMR in Biomedicine

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The objective of the present work was to improve data acquisition and quantification of dynamic contrast‐enhanced perfusion imaging in the in vivo murine heart. Four‐fold undersampled data were acquired in 14 mice and reconstructed using k‐t SPARSE. A two‐compartment exchange model was employed to provide additional characterization of myocardial tissue based on compartment volumes and the permeability surface area product. The feasibility of the proposed method was tested using compartment‐based analysis of contrast‐enhanced perfusion data acquired with intravascular and extracellular contrast agents. A significantly different permeability surface area product was measured for the intravascular versus extracellular contrast agent (0.13–0.15 ml/g/min vs 0.86–0.88 ml/g/min). The reduced extravasation also resulted in significantly smaller interstitial volumes of the intravascular versus extracellular agent (9.8–11% vs 45–47%). No difference was found for myocardial blood flow (6.5–7.2 ml/g/min vs 6.0–7.0 ml/g/min). The results presented here show that two‐compartment exchange modeling in the in vivo murine heart is feasible and gives access to tissue parameters beyond myocardial blood flow.

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Gadofosveset‐based biomarker of tissue albumin concentration: Technical validation in vitro and feasibility in vivo

Cited by 14 publications

References 59 publications

Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI

Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI

Gd-AAZTA-MADEC, an improved blood pool agent for DCE-MRI studies on mice on 1 T scanners

Extended quantitative dynamic contrast‐enhanced cardiac perfusion imaging in mice using accelerated data acquisition and spatially distributed, two‐compartment exchange modeling

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