Albumin labeled with Gd-DTPA as an intravascular, blood pool-enhancing agent for MR imaging: biodistribution and imaging studies.

Schmiedl, Udo P.; Ogan, Marc D.; Paajanen, Hannu; Marotti, Miljenko; Crooks, Lawrence E.; Brito, Anthony; Brasch, Robert C.

doi:10.1148/radiology.162.1.3786763

Cited by 206 publications

(104 citation statements)

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“…By comparison, the blood pool agent albumin(Gd-DTPA) 30 is largely retained in the intravascular space with a half-life of 88min after intravenous injection and can remain in the bloodtstream and extravascular compartment two weeks after injection. (77,78) These undesirably long retention times have precluded its use in the clinic.…”

Section: Resultsmentioning

confidence: 99%

Development of Contrast Agents Targeted to Macrophage Scavenger Receptors for MRI of Vascular Inflammation

2006

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Atherosclerosis is a leading cause of death in the U.S. Because there is a potential to prevent coronary and arterial diseases through early diagnosis, there is a need for methods to image arteries in the subclinical stage as well as clinical stage using various non-invasive techniques, including Magnetic Resonance Imaging (MRI). We describe a development of a novel MRI contrast agent targeted to plaques that will allow imaging of lesion formation. The contrast agent is directed to macrophages, one of the earliest components of developing plaques. Macrophages are labeled through the macrophage scavenger receptor A, a macrophage specific cell surface protein, using an MRI contrast agent derived from scavenger receptor ligands. We have synthesized and characterized these contrast agents with a range of relaxivities. In vitro studies show that the targeted contrast agent accumulates in macrophages and solution studies indicate that micromolar concentrations are sufficient to produce contrast in an MR image. Cell toxicity and initial biodistribution studies indicate low toxicity, no detectable retention in normal blood vessels, and rapid clearance from blood. The promising performance of this contrast agent targeted towards vascular inflammation opens doors to tracking of other inflammatory diseases such as tumor immunotherapy and transplant acceptance using MRI.

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Section: Resultsmentioning

confidence: 99%

Development of Contrast Agents Targeted to Macrophage Scavenger Receptors for MRI of Vascular Inflammation

2006

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“…Albumin-(Gd-DTPA)30is a prototype MMCM with a molecular weight of 92 kDa and an initial distribution volume of 0.05 I/kg, which closely ap proximates the blood volume [16] …”

Section: Contrastmediamentioning

confidence: 99%

Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media.

Daldrup¹,

Shames²,

Wendland³

et al. 1998

American Journal of Roentgenology

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240

203

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Quantitative assays of tumor microvascular characteristics based on dynamic MR imaging were correlated with histopathologic grade in mammary soft-tissue tumors. MATERIALS AND METHODS. A spectrum of tumors, benignthrough highlymalignant, was induced in 33 female rats by administration of N-ethyl-N-nitrosourea, a potent car cinogen. Dynamic contrast-enhanced MR imaging was performed using a small-molecular contrast medium (gadopentetate, molecular weight = 0.5 kDa) and a macromolecular contrast medium (albumin-(Gd-DTPA)30, molecular weight = 92 kDa) at an interval of 1â€"2 days. Per meability surface area product (PS), as estimated by the corresponding endothelial transfer coefficient (K@5), and fractional plasma volume (JPV) were calculated for each tumor and each contrast agent using a two-compartment bidirectional kinetic model. MR imaging mi crovascular characteristics were correlated with histopathologic tumor grade. RESULTS. Tumorpermeability to macromolecular contrast medium,characterized byK@5, showed a highly positive correlation with tumor grade (r2 = .76, p < lO_10). K@5 values were zero for all benign and some low-grade carcinomas, greater than zero in all other carci nomas, and increased in magnitude with higher tumor grade. A considerably smaller but sig nificantly positive correlation was found betweenfPV and tumor grade using macromolecular contrast medium (r2 = .25, p < .003). No correlation between K@5orfPV values and tumor grade was found using gadopentetate (r2 = .01, p > .95 and r2 = .03, p > .15, respectively).CONCLUSION. Quantitative tumormicrovascular permeability assays generated with macromolecular MR imaging contrast medium correlate closely with histologic tumor grade. No significant correlation is found using small-molecular gadopentetate. Parnassus Ave.,San Francisco, CA94143-0628. Address correspondence to R.C.Brasch.

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“…In addition, since Gd-DTPA relaxivity is also affected by magnetic field strength, temperature, and the macromolecule to which it is attached, direct comparison of our results with other studies is difficult. Schmiedl et al [32] reported a R 1 value for Gd-DTPA-Albumin (9 Gd-DTPA per albumin) to be 110 L/mmol-s measured at 0.25 T, 37 °C. Brasch [14] reported a R 1 value of 14.4 L/mmol-s per Gd for Albumin-Gd-DTPA at 0.25 T, 25 °C.…”

Section: Discussionmentioning

confidence: 99%

Quantitative assessment of macromolecular concentration during direct infusion into an agarose hydrogel phantom using contrast-enhanced MRI

Chen

Astary

Sepulveda

et al. 2008

Magnetic Resonance Imaging

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Convection-enhanced delivery (CED), i.e., direct tissue infusion, has emerged as a promising local drug delivery method for treating diseases of the nervous system. Determination of the spatial distribution of therapeutic agents after infusion is important in evaluating the efficacy of treatment, optimizing infusion protocols, and improving the understanding of drug pharmacokinetics. In this study, we provide a methodology to determine the concentration distribution of Gd-labeled tracers during infusion using contrast-enhanced MR imaging. To the best of our knowledge, MR studies that quantify concentration profiles for CED have not been previously reported. The methodology utilizes intrinsic material properties (T 1 and R 1 ) and reduces the effect of instrumental factors (e.g., inhomogeneity of MR detection field). As a methodology investigation, this study used an agarose hydrogel phantom as a tissue substitute for infusion. An 11.1 T magnet system was used to image infusion of Gd-DTPA labeled albumin (Gd-albumin) into the hydrogel. By using data from preliminary scans, Gd-albumin distribution was determined from the signal intensity of the MR images. As a validation test, MR-derived concentration profiles were found comparable to both results measured directly using quantitative optical imaging and results from a computational transport model in porous media. In future studies, the developed methodology will be used to quantitatively monitor the distribution of Gd-tracer following infusion directly into tissues.

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Albumin labeled with Gd-DTPA as an intravascular, blood pool-enhancing agent for MR imaging: biodistribution and imaging studies.

Cited by 206 publications

References 0 publications

Development of Contrast Agents Targeted to Macrophage Scavenger Receptors for MRI of Vascular Inflammation

Development of Contrast Agents Targeted to Macrophage Scavenger Receptors for MRI of Vascular Inflammation

Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media.

Quantitative assessment of macromolecular concentration during direct infusion into an agarose hydrogel phantom using contrast-enhanced MRI

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