| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1
Department of Radiology, Cleveland Clinic — Florida, 3000 W. Cypress
Creek Rd., Ft. Lauderdale, FL 33309.
2
Albany College of Pharmacy, Union University, 106 New Scotland AVe., Albany,
NY 12208.
3
Department of Radiology, Allegheny General Hospital, 320 E. North Ave.,
Pittsburgh, PA 15212.
Received November 23, 1999;
accepted after revision February 28, 2000.
Presented at the annual meeting of the American Roentgen Ray Society, New
Orleans, May 1999.
Abstract
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
MATERIALS AND METHODS. Mixtures of commercially available nonionic and ionic iodinated contrast agent, gadopentetate dimeglumine, lidocaine, and epinephrine were analyzed using a spectrophotometric titration with a gadolinium ion titrant and methyl thymol blue indicator.
RESULTS. We found no significant dissociation of gadolinium ion when gadopentetate dimeglumine was mixed with iodinated contrast agents, lidocaine, or epinephrine in any of the dilutions tested.
CONCLUSION. Gadopentetate dimeglumine and iodinated contrast material can be mixed before MR imaging without any release of free gadolinium and are therefore safe for confirming the intraarticular placement of contrast material before MR arthrography.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
In 1994, Kopka et al. [1] suggested mixing gadopentetate dimeglumine directly with iodinated contrast material for injection before MR arthrography but raised the question of the unknown interactions between the two contrast materials. Premixing the diluted gadopentetate dimeglumine with iodinated contrast material would improve delivery of the contrast agent to the joint and would require less patient manipulation, but the stability of the gadopentetate dimeglumine compound in the presence of iodinated contrast material needs to be assessed. Gadopentetate dimeglumine has proven to be systemically safe in several clinical trails [2, 3], and the effect of gadopentetate dimeglumine on joint structures has been shown to be negligible [4, 5]. However, the gadolinium ion is systemically toxic, with a lethal dose in half the population of 636 mmol/kg. The purpose of this study was to determine whether free gadolinium ion dissociates from the gadopentetate dimeglumine complex when gadopentetate dimeglumine is mixed with iodinated contrast agent or other solutions routinely injected during MR arthrography.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Methyl thymol blue (yellow) + gadolinium ionmethyl thymol blue—gadolinium complex (blue)
Note that although free methyl thymol blue is yellow, the methyl thymol blue—gadolinium complex is blue. Because the former exhibits a maximum absorbance at 425 nm and the latter at 605 nm (Fig. 1), measuring the absorbance at either of these wavelengths could monitor the progress of the titration. In this study, the absorbance at 605 nm was used.
|
Both radiographic and MR imaging contrast agents commonly contain metal complexing agents in addition to the contrast agent itself. Iodinated contrast agents typically contain small amounts of ethylenediamine tetraacetic acid (EDTA), whereas Magnevist contains a small excess of diethylenetriamine pentaacetic acid (DTPA) (Table 1). Because the binding affinities for gadolinium with these complexing agents are much stronger than those with methyl thymol blue, any gadolinium ion added to the solution during a titration or through a reaction that frees the gadolinium ion from its complex will preferentially combine with the DTPA or EDTA. Only when neither DTPA nor EDTA is present will the gadolinium ions bind with methyl thymol blue. As stated previously, this binding would be accompanied by a change in color of the solution from yellow to blue.
|
While the titrations were performed, small amounts of gadolinium ion were added to each solution being examined. The amount of gadolinium ion needed to reach the endpoint, or that point at which methyl thymol blue begins to bind gadolinium ions, provides an indirect measure of the amount of complexing agent present in the sample. The amount of complexing agent actually found in the solution titrated can be compared with the predicted amount and used to quantify and release the gadolinium ion from the gadopentetate dimeglumine complex. The general shape of the expected titration curve was expected to resemble the curve in Figure 2, in which the transition from region 1 to region 2 would indicate the experimental endpoint of the titration.
|
Seventeen sets of samples were prepared for analysis, each in triplicate (Table 2). Three iodinated contrast agents (Conray-43 [Mallinckrodt Medical, St. Louis, MO], Hypaque-60 [Nycomed, Princeton, NJ], and Isovue-M 200 [Bracco Diagnostics, Princeton, NJ]) were mixed with Magnevist (Table 1) at a concentration approximating that used during MR arthrography (1:20). Additional samples included the mixture of Conray-43 with Magnevist at a high concentration (1:1); the mixture of Conray-43, Magnevist, lidocaine, and epinephrine; and a mixture of Conray-43 and Magnevist incubated at 38°C for 24 hr. An incubation time of 24 hr was a conservative length of time because joint clearance of these compounds should occur before 24 hr [4]. Samples of each contrast agent alone in solution were also prepared and were used to determine the calculated endpoints.
|
Titrations were performed by adding gadolinium ions (as gadolinium chloride [Aldrich Chemical, Milwaukee, WI]) in small increments (1-30 µL) to a sample prepared in methyl methacrylate ultraviolet—visible cuvettes (Fisher Scientific, Pittsburgh, PA). After complete mixing, the absorbance at 605 nm was recorded on a Lambda 6 ultraviolet-visible spectrometer (model C688-0002; PerkinElmer, Norwalk, CT) at 1-nm resolution and a scanning speed of 120 nm/min. Heated samples were incubated in an oven for 24 hr at 38°C, allowed to cool, and then analyzed. After each titration, best-fit lines were drawn through the data points in regions 1 and 2 of the titration curve (Fig. 3). The intersection of these lines was taken as the experimental endpoint. Experimental endpoints were compared with calculated endpoints determined from the titration of unmixed contrast agents. All statistical calculations were performed at the 95% confidence level.
|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The high stability constant for the gadopentetate dimeglumine complex (1 x 1023) [7] indicates very strong binding and results in dissociation of the complex only under the most extreme conditions. The stability constant for the gadolinium-EDTA complex (2 x 1017) [7] is six orders of magnitude lower than that of the gadopentetate dimeglumine complex. This suggests that the dissociation of the gadopentetate dimeglumine complex could not be caused by the addition of EDTA. Similarly, it was expected that neither the iodinated contrast materials nor any of the other materials present in the mixtures prepared (saline, lidocaine, or epinephrine) would result in the release of free gadolinium ion in solution.
All but one of the mixtures tested showed no statistical difference between the calculated number of moles and the number of moles experimentally required to begin binding methyl thymol blue indicator. This finding indicates that no gadolinium ion dissociated from the gadopentetate dimeglumine complex. Although the Magnegist/Hypaque mixture did show a slight statistical difference, it is likely because of the relatively small number of replicates performed and would not indicate a true difference. This probability is supported by the fact that the samples containing Conray-43, which has a chemical structure virtually identical to that of Hypaque, showed no evidence of dissociation.
Although the results of this study did not show the formation of free gadolinium ions in the mixtures tested, the extension of these results to predict in vivo safety has several limitations. First, these experiments were not designed to detect the presence of other potentially toxic gadolinium compounds that might be formed by the interaction of contrast agents. Second, this study examined the mixtures before injection and would not account for any reactions that may occur with the components of synovial fluid after injection.
In conclusion, Magnevist can be mixed with either ionic or nonionic contrast agents before MR imaging without any release of free gadolinium ions. Epinephrine, lidocaine, or both can be added to the mixture as desired without concern for gadopentetate dimeglumine dissociation. Mixing these contrast agents will facilitate delivery of intraarticular contrast material and may provide additional helpful information before MR imaging.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Andreisek, J. M. Froehlich, J. Hodler, D. Weishaupt, V. Beutler, C. W. A. Pfirrmann, C. Boesch, and D. Nanz Direct MR Arthrography at 1.5 and 3.0 T: Signal Dependence on Gadolinium and Iodine Concentrations--Phantom Study Radiology, June 1, 2008; 247(3): 706 - 716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. H. Theumann, G. Etechami, B. Duvoisin, M. Wintermark, P. Schnyder, N. Favarger, and L. A. Gilula Association between Extrinsic and Intrinsic Carpal Ligament Injuries at MR Arthrography and Carpal Instability at Radiography: Initial Observations Radiology, March 1, 2006; 238(3): 950 - 957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. P. Sundberg, G. A. Toomayan, and N. M. Major Evaluation of the Acetabular Labrum at 3.0-T MR Imaging Compared with 1.5-T MR Arthrography: Preliminary Experience Radiology, February 1, 2006; 238(2): 706 - 711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Masi, D. Newitt, C. A. Sell, H. Daldrup-Link, L. Steinbach, S. Majumdar, and T. M. Link Optimization of Gadodiamide Concentration for MR Arthrography at 3 T Am. J. Roentgenol., June 1, 2005; 184(6): 1754 - 1761. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
